49 results on '"Folegatti, Pedro M."'
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2. Reactogenicity and immunogenicity after a late second dose or a third dose of ChAdOx1 nCoV-19 in the UK: a substudy of two randomised controlled trials (COV001 and COV002)
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Adlou, Syed, Aley, Robert, Ali, Aabidah, Anslow, Rachel, Baker, Megan, Baker, Phillip, Barrett, Jordan R., Bates, Louise, Beadon, Kirsten, Beckley, Rebecca, Bell, Jonathan, Bellamy, Duncan, Beveridge, Amy, Bissett, Cameron, Blackwell, Luke, Bletchly, Heather, Boyd, Amy, Bridges-Webb, Alice, Brown, Charlie, Byard, Nicholas, Camara, Susana, Cifuentes Gutierrez, Liliana, Collins, Andrea M., Cooper, Rachel, Crocker, Wendy E.M., Darton, Thomas C., Davies, Hannah, Davies, Judith, Demissie, Tesfaye, Di Maso, Claudio, Dinesh, Tanya, Donnellan, Francesca R., Douglas, Alexander D., Drake-Brockman, Rachael, Duncan, Christopher J.A., Elias, Sean C., Emary, Katherine R.W., Ghulam Farooq, Mutjaba, Faust, Saul N., Felle, Sally, Ferreira, Daniela, Ferreira Da Silva, Carla, Finn, Adam, Ford, Karen J., Francis, Emma, Furze, Julie, Fuskova, Michelle, Galiza, Eva, Gibertoni Cruz, Ana, Godfrey, Leila, Goodman, Anna L., Green, Catherine, Green, Christopher A., Greenwood, Nicola, Harrison, Daisy, Hart, Thomas C., Hawkins, Sophia, Heath, Paul T., Hill, Helen, Hillson, Kushalinii, Horsington, Bryn, Hou, Mimi M., Howe, Elizabeth, Howell, Nicola, Joe, Carina, Jones, Elizabeth, Kasanyinga, Mwila, Keen, Jade, Kelly, Sarah, Kerr, David, Khan, Liaquat, Khozoee, Baktash, Kinch, Jasmin, Kinch, Patrick, Koleva, Stanislava, Kwok, Jonathan, Larkworthy, Colin W., Lawrie, Alison M., Lazarus, Rajeka, Lees, Emily A., Li, Grace, Libri, Vincenzo, Lillie, Patrick J., Linder, Aline, Long, Fei, Lopez Ramon, Raquel, Mabbett, Reece, Makinson, Rebecca, Marinou, Spyridoula, Marlow, Emma, Marshall, Julia L., Mazur, Olga, McEwan, Joanne, McGregor, Alastair C., Mokaya, Jolynne, Morey, Ella, Morshead, Gertraud, Morter, Richard, Muller, Jilly, Mweu, Philomena, Noristani, Rabiullah, Owino, Nelly, Polo Peralta Alvarez, Marco, Platt, Abigail, Pollock, Katrina M., Poulton, Ian, Provstgaard-Morys, Samuel, Pulido-Gomez, David, Rajan, Matthew, Ramos Lopez, Fernando, Ritchie, Adam, Roberts, Hannah, Rollier, Christine, Rudiansyah, Indra, Sanders, Katherine, Saunders, Jack E., Seddiqi, Samiullah, Sharpe, Hannah R., Shaw, Robert, Silva-Reyes, Laura, Singh, Nisha, Smith, David J., Smith, Catherine C., Smith, Andrew, Spencer, Alexandra J., Stuart, Arabella S.V., Sutherland, Rebecca, Szigeti, Anna, Tang, Karly, Thomas, Merin, Thomas, Tonia M., Thompson, Amber, Thomson, Emma C., Török, Estée M., Toshner, Mark, Tran, Nguyen, Trivett, Rose, Turnbull, Iain, Turner, Cheryl, Turner, David P.J., Ulaszewska, Marta, Vichos, Iason, Walker, Laura, Watson, Marion E., Whelan, Conor, White, Rachel, Williams, Sarah J., Williams, Christopher J.A., Wright, Daniel, Yao, Andy, Flaxman, Amy, Marchevsky, Natalie G, Jenkin, Daniel, Aboagye, Jeremy, Aley, Parvinder K, Angus, Brian, Belij-Rammerstorfer, Sandra, Bibi, Sagida, Bittaye, Mustapha, Cappuccini, Federica, Cicconi, Paola, Clutterbuck, Elizabeth A, Davies, Sophie, Dejnirattisai, Wanwisa, Dold, Christina, Ewer, Katie J, Folegatti, Pedro M, Fowler, Jamie, Hill, Adrian V S, Kerridge, Simon, Minassian, Angela M, Mongkolsapaya, Juthathip, Mujadidi, Yama F, Plested, Emma, Ramasamy, Maheshi N, Robinson, Hannah, Sanders, Helen, Sheehan, Emma, Smith, Holly, Snape, Matthew D, Song, Rinn, Woods, Danielle, Screaton, Gavin, Gilbert, Sarah C, Voysey, Merryn, Pollard, Andrew J, and Lambe, Teresa
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- 2021
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3. Safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 in HIV infection: a single-arm substudy of a phase 2/3 clinical trial
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Watson, Marion E.E., Song, Rinn, Cicconi, Paola, Minassian, Angela M., Bibi, Sagida, Kerridge, Simon, Singh, Nisha, Green, Catherine M., Douglas, Alexander D., Lawrie, Alison M., Clutterbuck, Elizabeth A., Frater, John, Ewer, Katie J, Ogbe, Ane, Pace, Mathew, Adele, Sandra, Adland, Emily, Alagaratnam, Jasmini, Aley, Parvinder K, Ali, Mohammad, Ansari, M Azim, Bara, Anna, Bittaye, Mustapha, Broadhead, Samantha, Brown, Anthony, Brown, Helen, Cappuccini, Federica, Cooney, Enya, Dejnirattisai, Wanwisa, Dold, Christina, Fairhead, Cassandra, Fok, Henry, Folegatti, Pedro M, Fowler, Jamie, Gibbs, Charlotte, Goodman, Anna L, Jenkin, Daniel, Jones, Mathew, Makinson, Rebecca, Marchevsky, Natalie G, Mujadidi, Yama F, Nguyen, Hanna, Parolini, Lucia, Petersen, Claire, Plested, Emma, Pollock, Katrina M, Ramasamy, Maheshi N, Rhead, Sarah, Robinson, Hannah, Robinson, Nicola, Rongkard, Patpong, Ryan, Fiona, Serrano, Sonia, Tipoe, Timothy, Voysey, Merryn, Waters, Anele, Zacharopoulou, Panagiota, Barnes, Eleanor, Dunachie, Susanna, Goulder, Philip, Klenerman, Paul, Screaton, Gavin R, Winston, Alan, Hill, Adrian V S, Gilbert, Sarah C, Pollard, Andrew J, Fidler, Sarah, Fox, Julie, and Lambe, Teresa
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- 2021
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4. Reduced blood-stage malaria growth and immune correlates in humans following RH5 vaccination
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Minassian, Angela M., Silk, Sarah E., Barrett, Jordan R., Nielsen, Carolyn M., Miura, Kazutoyo, Diouf, Ababacar, Loos, Carolin, Fallon, Jonathan K., Michell, Ashlin R., White, Michael T., Edwards, Nick J., Poulton, Ian D., Mitton, Celia H., Payne, Ruth O., Marks, Michael, Maxwell-Scott, Hector, Querol-Rubiera, Antonio, Bisnauthsing, Karen, Batra, Rahul, Ogrina, Tatiana, Brendish, Nathan J., Themistocleous, Yrene, Rawlinson, Thomas A., Ellis, Katherine J., Quinkert, Doris, Baker, Megan, Lopez Ramon, Raquel, Ramos Lopez, Fernando, Barfod, Lea, Folegatti, Pedro M., Silman, Daniel, Datoo, Mehreen, Taylor, Iona J., Jin, Jing, Pulido, David, Douglas, Alexander D., de Jongh, Willem A., Smith, Robert, Berrie, Eleanor, Noe, Amy R., Diggs, Carter L., Soisson, Lorraine A., Ashfield, Rebecca, Faust, Saul N., Goodman, Anna L., Lawrie, Alison M., Nugent, Fay L., Alter, Galit, Long, Carole A., and Draper, Simon J.
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- 2021
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5. Phase 1/2 trial of SARS-CoV-2 vaccine ChAdOx1 nCoV-19 with a booster dose induces multifunctional antibody responses
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Barrett, Jordan R., Belij-Rammerstorfer, Sandra, Dold, Christina, Ewer, Katie J., Folegatti, Pedro M., Gilbride, Ciaran, Halkerston, Rachel, Hill, Jennifer, Jenkin, Daniel, Stockdale, Lisa, Verheul, Marije K., Aley, Parvinder K., Angus, Brian, Bellamy, Duncan, Berrie, Eleanor, Bibi, Sagida, and Bittaye, Mustapha
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AstraZeneca PLC -- Product development ,Immune response -- Health aspects ,Viral antibodies -- Health aspects ,Antibodies -- Health aspects ,Pharmaceutical industry -- Product development ,Biological sciences ,Health ,AZD1222 (Vaccine) -- Physiological aspects -- Testing - Abstract
More than 190 vaccines are currently in development to prevent infection by the novel severe acute respiratory syndrome coronavirus 2. Animal studies suggest that while neutralizing antibodies against the viral spike protein may correlate with protection, additional antibody functions may also be important in preventing infection. Previously, we reported early immunogenicity and safety outcomes of a viral vector coronavirus vaccine, ChAdOx1 nCoV-19 (AZD1222), in a single-blinded phase 1/2 randomized controlled trial of healthy adults aged 18-55 years (NCT04324606). Now we describe safety and exploratory humoral and cellular immunogenicity of the vaccine, from subgroups of volunteers in that trial, who were subsequently allocated to receive a homologous full-dose (SD/SD D56; n = 20) or half-dose (SD/LD D56; n = 32) ChAdOx1 booster vaccine 56 d following prime vaccination. Previously reported immunogenicity data from the open-label 28-d interval prime-boost group (SD/SD D28; n = 10) are also presented to facilitate comparison. Additionally, we describe volunteers boosted with the comparator vaccine (MenACWY; n = 10). In this interim report, we demonstrate that a booster dose of ChAdOx1 nCoV-19 is safe and better tolerated than priming doses. Using a systems serology approach we also demonstrate that anti-spike neutralizing antibody titers, as well as Fc-mediated functional antibody responses, including antibody-dependent neutrophil/monocyte phagocytosis, complement activation and natural killer cell activation, are substantially enhanced by a booster dose of vaccine. A booster dose of vaccine induced stronger antibody responses than a dose-sparing half-dose boost, although the magnitude of T cell responses did not increase with either boost dose. These data support the two-dose vaccine regime that is now being evaluated in phase 3 clinical trials. Two doses of the coronavirus disease 2019 vaccine ChAdOx1 nCoV-19 boost antibody responses and functions in phase 1/2 trial participants., Author(s): Jordan R. Barrett [sup.1] , Sandra Belij-Rammerstorfer [sup.1] , Christina Dold [sup.2] , Katie J. Ewer [sup.1] , Pedro M. Folegatti [sup.1] , Ciaran Gilbride [sup.1] , Rachel Halkerston [...]
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- 2021
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6. Safety and immunogenicity of a candidate Middle East respiratory syndrome coronavirus viral-vectored vaccine: a dose-escalation, open-label, non-randomised, uncontrolled, phase 1 trial
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Folegatti, Pedro M, Bittaye, Mustapha, Flaxman, Amy, Lopez, Fernando Ramos, Bellamy, Duncan, Kupke, Alexandra, Mair, Catherine, Makinson, Rebecca, Sheridan, Jonathan, Rohde, Cornelius, Halwe, Sandro, Jeong, Yuji, Park, Young-Shin, Kim, Jae-Ouk, Song, Manki, Boyd, Amy, Tran, Nguyen, Silman, Daniel, Poulton, Ian, Datoo, Mehreen, Marshall, Julia, Themistocleous, Yrene, Lawrie, Alison, Roberts, Rachel, Berrie, Eleanor, Becker, Stephan, Lambe, Teresa, Hill, Adrian, Ewer, Katie, and Gilbert, Sarah
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- 2020
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7. A single dose of ChAdOx1 Chik vaccine induces neutralizing antibodies against four chikungunya virus lineages in a phase 1 clinical trial
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Folegatti, Pedro M., Harrison, Kate, Preciado-Llanes, Lorena, Lopez, Fernando Ramos, Bittaye, Mustapha, Kim, Young Chan, Flaxman, Amy, Bellamy, Duncan, Makinson, Rebecca, Sheridan, Jonathan, Azar, Sasha R., Campos, Rafael Kroon, Tilley, Mark, Tran, Nguyen, Jenkin, Daniel, Poulton, Ian, Lawrie, Alison, Roberts, Rachel, Berrie, Eleanor, Rossi, Shannan L., Hill, Adrian, Ewer, Katie J., and Reyes-Sandoval, Arturo
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- 2021
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8. Persistence of the immune response after two doses of ChAdOx1 nCov-19 (AZD1222): 1 year of follow-up of two randomized controlled trials
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Voysey, Merryn, primary, Flaxman, Amy, additional, Aboagye, Jeremy, additional, Aley, Parvinder K, additional, Belij-Rammerstorfer, Sandra, additional, Bibi, Sagida, additional, Bittaye, Mustapha, additional, Cappuccini, Federica, additional, Charlton, Sue, additional, Clutterbuck, Elizabeth A, additional, Davies, Sophie, additional, Dold, Christina, additional, Edwards, Nick J, additional, Ewer, Katie J, additional, Faust, Saul N, additional, Folegatti, Pedro M, additional, Fowler, Jamie, additional, Gilbride, Ciaran, additional, Gilbert, Sarah C, additional, Godfrey, Leila, additional, Hallis, Bassam, additional, Humphries, Holly E, additional, Jenkin, Daniel, additional, Kerridge, Simon, additional, Mujadidi, Yama F, additional, Plested, Emma, additional, Ramasamy, Maheshi N, additional, Robinson, Hannah, additional, Sanders, Helen, additional, Snape, Matthew D, additional, Song, Rinn, additional, Thomas, Kelly M, additional, Ulaszewska, Marta, additional, Woods, Danielle, additional, Wright, Daniel, additional, Pollard, Andrew J, additional, and Lambe, Teresa, additional
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- 2023
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9. Single Dose Administration, And The Influence Of The Timing Of The Booster Dose On Immunogenicity and Efficacy Of ChAdOx1 nCoV-19 (AZD1222) Vaccine
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Voysey, Merryn, Costa Clemens, Sue Ann, Madhi, Shabir A, Weckx, Lily Yin, Folegatti, Pedro M, Aley, Parvinder K, Angus, Brian John, Baillie, Vicky, Barnabas, Shaun L, Bhorat, Qasim E, Bibi, Sagida, Briner, Carmen, Cicconi, Paola, Clutterbuck, Elizabeth, Collins, Andrea M, Cutland, Clare, Darton, Thomas, Dheda, Keertan, Douglas, Alexander D, Duncan, Christopher JA, Emary, Katherine RW, Ewer, Katie, Flaxman, Amy, Fairlie, Lee, Faust, Saul N, Feng, Shuo, Ferreira, Daniela M, Finn, Adam, Galiza, Eva, Goodman, Anna L, Green, Catherine M, Green, Christopher A, Greenland, Melanie, Hill, Catherine, Hill, Helen C, Hirsch, Ian, Izu, Alane, Jenkin, Daniel, Kerridge, Simon, Koen, Anthonet, Kwatra, Gaurav, Lazarus, Rajeka, Libri, Vincenzo, Lillie, Patrick J, Marchevsky, Natalie, Marshall, Richard P, Mendes, Ana Verena Almeida, Milan, Eveline P, Minassian, Angela M, McGregor, Alastair C, Farooq Mujadidi, Yama, Nana, Anusha, Payadachee, Sherman D, Phillips, Daniel J, Pittella, Ana, Plested, Emma, Pollock, Katrina M, Ramasamy, Maheshi N, Robinson, Hannah, Schwarzbold, Alexandre V, Smith, Andrew, Song, Rinn, Snape, Matthew D, Sprinz, Eduardo, Sutherland, Rebecca K, Thomson, Emma C, Török, Mili Estée, Toshner, Mark, Turner, David PJ, Vekemans, Johan, Villafana, Tonya L, White, Thomas, Williams, Christopher J, Hill, Adrian VS, Lambe, Teresa, Gilbert, Sarah C, Pollard, Andrew, and Group, Oxford COVID Vaccine Trial
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- 2022
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10. Efficacy of ChAdOx1 nCoV-19 (AZD1222) Vaccine Against SARS-CoV-2 VOC 202012/01 (B.1.1.7)
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Emary, Katherine RW, Golubchik, Tanya, Aley, Parvinder K, Ariani, Cristina V, Angus, Brian John, Bibi, Sagida, Blane, Beth, Bonsall, David, Cicconi, Paola, Charlton, Sue, Clutterbuck, Elizabeth, Collins, Andrea M, Cox, Tony, Darton, Thomas, Dold, Christina, Douglas, Alexander D, Duncan, Christopher JA, Ewer, Katie, Flaxman, Amy, Faust, Saul N, Ferreira, Daniela M, Feng, Shuo, Finn, Adam, Folegatti, Pedro M, Fuskova, Michelle, Galiza, Eva, Goodman, Anna L, Green, Catherine M, Green, Christopher A, Greenland, Melanie, Hallis, Bassam, Heath, Paul T, Hay, Jodie, Hill, Helen C, Jenkin, Daniel, Kerridge, Simon, Lazarus, Rajeka, Libri, Vincenzo, Lillie, Patrick J, Ludden, Catherine, Marchevsky, Natalie, Minassian, Angela M, McGregor, Alastair C, Farooq Mujadidi, Yama, Phillips, Daniel J, Plested, Emma, Pollock, Katrina M, Robinson, Hannah, Smith, Andrew, Song, Rinn, Snape, Matthew D, Sutherland, Rebecca K, Thomson, Emma C, Toshner, Mark, Turner, David PJ, Vekemans, Johan, Villafana, Tonya L, Williams, Christopher J, Hill, Adrian VS, Lambe, Teresa, Gilbert, Sarah C, Voysey, Merryn, Ramasamy, Maheshi N, Pollard, Andrew, Consortium, COVID-19 Genomics UK COG-UK, and Group, Oxford COVID Vaccine Trial
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- 2022
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11. Repeat controlled human malaria infection of healthy UK adults with blood-stage Plasmodium falciparum: Safety and parasite growth dynamics
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Salkeld, Jo, primary, Themistocleous, Yrene, additional, Barrett, Jordan R., additional, Mitton, Celia H., additional, Rawlinson, Thomas A., additional, Payne, Ruth O., additional, Hou, Mimi M., additional, Khozoee, Baktash, additional, Edwards, Nick J., additional, Nielsen, Carolyn M., additional, Sandoval, Diana Muñoz, additional, Bach, Florian A., additional, Nahrendorf, Wiebke, additional, Ramon, Raquel Lopez, additional, Baker, Megan, additional, Ramos-Lopez, Fernando, additional, Folegatti, Pedro M., additional, Quinkert, Doris, additional, Ellis, Katherine J., additional, Poulton, Ian D., additional, Lawrie, Alison M., additional, Cho, Jee-Sun, additional, Nugent, Fay L., additional, Spence, Philip J., additional, Silk, Sarah E., additional, Draper, Simon J., additional, and Minassian, Angela M., additional
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- 2022
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12. Vaccines based on the replication-deficient simian adenoviral vector ChAdOx1: Standardized template with key considerations for a risk/benefit assessment
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Folegatti, Pedro M, primary, Jenkin, Daniel, additional, Morris, Susan, additional, Gilbert, Sarah, additional, Kim, Denny, additional, Robertson, James S., additional, Smith, Emily R., additional, Martin, Emalee, additional, Gurwith, Marc, additional, and Chen, Robert T., additional
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- 2022
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13. Repeat controlled human malaria infection of healthy UK adults with blood-stagePlasmodium falciparum: safety and parasite growth dynamics
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Salkeld, Jo, primary, Themistocleous, Yrene, additional, Barrett, Jordan R., additional, Mitton, Celia H., additional, Rawlinson, Thomas A., additional, Payne, Ruth O., additional, Hou, Mimi M., additional, Khozoee, Baktash, additional, Edwards, Nick J., additional, Nielsen, Carolyn M., additional, Sandoval, Diana Muñoz, additional, Bach, Florian A., additional, Nahrendorf, Wiebke, additional, Ramon, Raquel Lopez, additional, Baker, Megan, additional, Ramos-Lopez, Fernando, additional, Folegatti, Pedro M., additional, Quinkert, Doris, additional, Ellis, Katherine J., additional, Poulton, Ian D., additional, Lawrie, Alison M., additional, Cho, Jee-Sun, additional, Nugent, Fay L., additional, Spence, Philip J., additional, Silk, Sarah E., additional, Draper, Simon J., additional, and Minassian, Angela M., additional
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- 2022
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14. Highly sensitive lineage discrimination of SARS-CoV-2 variants through allele-specific probe PCR
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Ratcliff, Jeremy, Al-Beidh, Farah, Bibi, Sagida, Bonsall, David, Costa Clemens, Sue Ann, Estcourt, Lise, Evans, Amy, Fish, Matthew, Folegatti, Pedro M, Gordon, Anthony C, Jay, Cecilia, Jennings, Aislinn, Laing, Emma, Lambe, Teresa, MacIntyre-Cockett, George, Menon, David, Mouncey, Paul R, Nguyen, Dung, Pollard, Andrew J, Ramasamy, Maheshi N, Roberts, David J, Rowan, Kathryn M, Rynne, Jennifer, Shankar-Hari, Manu, Williams, Sarah, Harvala, Heli, Golubchik, Tanya, Simmonds, Peter, AMPHEUS Project, REMAP-CAP Immunoglobulin Domain UK Investigators, NIHR, Ratcliff, Jeremy [0000-0001-6522-138X], Bonsall, David [0000-0003-2187-0550], Jay, Cecilia [0000-0003-2387-9225], Shankar-Hari, Manu [0000-0002-5338-2538], Golubchik, Tanya [0000-0003-2765-9828], Simmonds, Peter [0000-0002-7964-4700], Apollo - University of Cambridge Repository, Project, AMPHEUS, Investigators, REMAP-CAP Immunoglobulin Domain UK, and Group, Oxford COVID-19 Vaccine Trial
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Microbiology (medical) ,allele-specific probe PCR ,SARS-CoV-2 ,viruses ,COVID-19 ,AMPHEUS Project, REMAP-CAP Immunoglobulin Domain UK Investigators, and Oxford COVID-19 Vaccine Trial Group ,06 Biological Sciences ,variants of concern ,Polymerase Chain Reaction ,Microbiology ,07 Agricultural and Veterinary Sciences ,diagnostics ,Humans ,next-generation sequencing ,variant identification ,Alleles ,11 Medical and Health Sciences - Abstract
Tools to detect SARS-CoV-2 variants of concern and track the ongoing evolution of the virus are necessary to support public health efforts and the design and evaluation of novel COVID-19 therapeutics and vaccines. Although next-generation sequencing (NGS) has been adopted as the gold standard method for discriminating SARS-CoV-2 lineages, alternative methods may be required when processing samples with low viral loads or low RNA quality. To this aim, an allele-specific probe PCR (ASP-PCR) targeting lineage-specific single nucleotide polymorphisms (SNPs) was developed and used to screen 1,082 samples from two clinical trials in the United Kingdom and Brazil. Probit regression models were developed to compare ASP-PCR performance against 1,771 NGS results for the same cohorts. Individual SNPs were shown to readily identify specific variants of concern. ASP-PCR was shown to discriminate SARS-CoV-2 lineages with a higher likelihood than NGS over a wide range of viral loads. The comparative advantage for ASP-PCR over NGS was most pronounced in samples with cycle threshold (CT) values between 26 and 30 and in samples that showed evidence of degradation. Results for samples screened by ASP-PCR and NGS showed 99% concordant results. ASP-PCR is well suited to augment but not replace NGS. The method can differentiate SARS-CoV-2 lineages with high accuracy and would be best deployed to screen samples with lower viral loads or that may suffer from degradation. Future work should investigate further destabilization from primer-target base mismatch through altered oligonucleotide chemistry or chemical additives.
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- 2022
15. Highly Sensitive Lineage Discrimination of SARS-CoV-2 Variants through Allele-Specific Probe PCR
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Ratcliff, Jeremy, primary, Al-Beidh, Farah, additional, Bibi, Sagida, additional, Bonsall, David, additional, Costa Clemens, Sue Ann, additional, Estcourt, Lise, additional, Evans, Amy, additional, Fish, Matthew, additional, Folegatti, Pedro M., additional, Gordon, Anthony C., additional, Jay, Cecilia, additional, Jennings, Aislinn, additional, Laing, Emma, additional, Lambe, Teresa, additional, MacIntyre-Cockett, George, additional, Menon, David, additional, Mouncey, Paul R., additional, Nguyen, Dung, additional, Pollard, Andrew J., additional, Ramasamy, Maheshi N., additional, Roberts, David J., additional, Rowan, Kathryn M., additional, Rynne, Jennifer, additional, Shankar-Hari, Manu, additional, Williams, Sarah, additional, Harvala, Heli, additional, Golubchik, Tanya, additional, and Simmonds, Peter, additional
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- 2022
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16. Durability of ChAdOx1 nCoV-19 vaccination in people living with HIV
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Ogbe, Ane, primary, Pace, Matthew, additional, Bittaye, Mustapha, additional, Tipoe, Timothy, additional, Adele, Sandra, additional, Alagaratnam, Jasmini, additional, Aley, Parvinder K., additional, Ansari, M. Azim, additional, Bara, Anna, additional, Broadhead, Samantha, additional, Brown, Anthony, additional, Brown, Helen, additional, Cappuccini, Federica, additional, Cinardo, Paola, additional, Dejnirattisai, Wanwisa, additional, Ewer, Katie J., additional, Fok, Henry, additional, Folegatti, Pedro M., additional, Fowler, Jamie, additional, Godfrey, Leila, additional, Goodman, Anna L., additional, Jackson, Bethany, additional, Jenkin, Daniel, additional, Jones, Mathew, additional, Longet, Stephanie, additional, Makinson, Rebecca A., additional, Marchevsky, Natalie G., additional, Mathew, Moncy, additional, Mazzella, Andrea, additional, Mujadidi, Yama F., additional, Parolini, Lucia, additional, Petersen, Claire, additional, Plested, Emma, additional, Pollock, Katrina M., additional, Rajeswaran, Thurkka, additional, Ramasamy, Maheshi N., additional, Rhead, Sarah, additional, Robinson, Hannah, additional, Robinson, Nicola, additional, Sanders, Helen, additional, Serrano, Sonia, additional, Tipton, Tom, additional, Waters, Anele, additional, Zacharopoulou, Panagiota, additional, Barnes, Eleanor, additional, Dunachie, Susanna, additional, Goulder, Philip, additional, Klenerman, Paul, additional, Screaton, Gavin R., additional, Winston, Alan, additional, Hill, Adrian V.S., additional, Gilbert, Sarah C., additional, Carroll, Miles, additional, Pollard, Andrew J., additional, Fidler, Sarah, additional, Fox, Julie, additional, Lambe, Teresa, additional, and Frater, John, additional
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- 2022
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17. Reactogenicity and immunogenicity after a late second dose or a third dose of ChAdOx1 nCoV-19 in the UK: a substudy of two randomised controlled trials (COV001 and COV002)
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Flaxman, Amy, Marchevsky, Natalie G, Jenkin, Daniel, Aboagye, Jeremy, Aley, Parvinder K, Angus, Brian, Belij-Rammerstorfer, Sandra, Bibi, Sagida, Bittaye, Mustapha, Cappuccini, Federica, Cicconi, Paola, Clutterbuck, Elizabeth A, Davies, Sophie, Dejnirattisai, Wanwisa, Dold, Christina, Ewer, Katie J, Folegatti, Pedro M, Fowler, Jamie, Hill, Adrian VS, Kerridge, Simon, Minassian, Angela M, Mongkolsapaya, Juthathip, Mujadidi, Yama F, Plested, Emma, Ramasamy, Maheshi N, Robinson, Hannah, Sanders, Helen, Sheehan, Emma, Smith, Holly, Snape, Matthew D, Song, Rinn, Woods, Danielle, Screaton, Gavin, Gilbert, Sarah C, Voysey, Merryn, Pollard, Andrew J, Lambe, Teresa, and Oxford COVID Vaccine Trial group
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BACKGROUND: COVID-19 vaccine supply shortages are causing concerns about compromised immunity in some countries as the interval between the first and second dose becomes longer. Conversely, countries with no supply constraints are considering administering a third dose. We assessed the persistence of immunogenicity after a single dose of ChAdOx1 nCoV-19 (AZD1222), immunity after an extended interval (44-45 weeks) between the first and second dose, and response to a third dose as a booster given 28-38 weeks after the second dose. METHODS: In this substudy, volunteers aged 18-55 years who were enrolled in the phase 1/2 (COV001) controlled trial in the UK and had received either a single dose or two doses of 5 × 1010 viral particles were invited back for vaccination. Here we report the reactogenicity and immunogenicity of a delayed second dose (44-45 weeks after first dose) or a third dose of the vaccine (28-38 weeks after second dose). Data from volunteers aged 18-55 years who were enrolled in either the phase 1/2 (COV001) or phase 2/3 (COV002), single-blinded, randomised controlled trials of ChAdOx1 nCoV-19 and who had previously received a single dose or two doses of 5 × 1010 viral particles are used for comparison purposes. COV001 is registered with ClinicalTrials.gov, NCT04324606, and ISRCTN, 15281137, and COV002 is registered with ClinicalTrials.gov, NCT04400838, and ISRCTN, 15281137, and both are continuing but not recruiting. FINDINGS: Between March 11 and 21, 2021, 90 participants were enrolled in the third-dose boost substudy, of whom 80 (89%) were assessable for reactogenicity, 75 (83%) were assessable for evaluation of antibodies, and 15 (17%) were assessable for T-cells responses. The two-dose cohort comprised 321 participants who had reactogenicity data (with prime-boost interval of 8-12 weeks: 267 [83%] of 321; 15-25 weeks: 24 [7%]; or 44-45 weeks: 30 [9%]) and 261 who had immunogenicity data (interval of 8-12 weeks: 115 [44%] of 261; 15-25 weeks: 116 [44%]; and 44-45 weeks: 30 [11%]). 480 participants from the single-dose cohort were assessable for immunogenicity up to 44-45 weeks after vaccination. Antibody titres after a single dose measured approximately 320 days after vaccination remained higher than the titres measured at baseline (geometric mean titre of 66·00 ELISA units [EUs; 95% CI 47·83-91·08] vs 1·75 EUs [1·60-1·93]). 32 participants received a late second dose of vaccine 44-45 weeks after the first dose, of whom 30 were included in immunogenicity and reactogenicity analyses. Antibody titres were higher 28 days after vaccination in those with a longer interval between first and second dose than for those with a short interval (median total IgG titre: 923 EUs [IQR 525-1764] with an 8-12 week interval; 1860 EUs [917-4934] with a 15-25 week interval; and 3738 EUs [1824-6625] with a 44-45 week interval). Among participants who received a third dose of vaccine, antibody titres (measured in 73 [81%] participants for whom samples were available) were significantly higher 28 days after a third dose (median total IgG titre: 3746 EUs [IQR 2047-6420]) than 28 days after a second dose (median 1792 EUs [IQR 899-4634]; Wilcoxon signed rank test p=0·0043). T-cell responses were also boosted after a third dose (median response increased from 200 spot forming units [SFUs] per million peripheral blood mononuclear cells [PBMCs; IQR 127-389] immediately before the third dose to 399 SFUs per milion PBMCs [314-662] by day 28 after the third dose; Wilcoxon signed rank test p=0·012). Reactogenicity after a late second dose or a third dose was lower than reactogenicity after a first dose. INTERPRETATION: An extended interval before the second dose of ChAdOx1 nCoV-19 leads to increased antibody titres. A third dose of ChAdOx1 nCoV-19 induces antibodies to a level that correlates with high efficacy after second dose and boosts T-cell responses. FUNDING: UK Research and Innovation, Engineering and Physical Sciences Research Council, National Institute for Health Research, Coalition for Epidemic Preparedness Innovations, National Institute for Health Research Oxford Biomedical Research Centre, Chinese Academy of Medical Sciences Innovation Fund for Medical Science, Thames Valley and South Midlands NIHR Clinical Research Network, AstraZeneca, and Wellcome.
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- 2021
18. T-cell mediated immunity after AZD1222 vaccination: A polyfunctional spike-specific Th1 response with a diverse TCR repertoire
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Swanson, Phillip A., Padilla, Marcelino, Hoyland, Wesley, McGlinchey, Kelly, Fields, Paul A., Bibi, Sagida, Faust, Saul N., McDermott, Adrian B., Lambe, Teresa, Pollard, Andrew J., Durham, Nicholas M., Kelly, Elizabeth J., Adlou, Syed, Aley, Parvinder K., Angus, Brian, Anslow, Rachel, Baker, Philip, Bansal, Himanshu, Beveridge, Amy, Bridges-Webb, Alice, Ching, Steven, Cicconi, Paola, Clutterbuck, Elizabeth A., Collins, Andrea M., Darton, Thomas C., Demissie, Tesfaye, Dinesh, Tanya, Douglas, Alexander D., Duncan, Christopher J. A., Ewer, Katie J., Felle, Sally, Finn, Adam, Folegatti, Pedro M., Fuskova, Michelle, Gilbert, Sarah C., Goodman, Anna, Green, Christopher A., Harbolick, Elizabeth, Hart, Thomas C., Hayes, Susana, Hill, Adrian V. S., Jenkin, Daniel, Jepson, Brett M., Kasanyinga, Mwila, Kerridge, Simon, Libri, Vincenzo, Lillie, Patrick J., McGregor, Alastair C., Minassian, Angela M., Mujadidi, Yama F., Pilataxi, Fernanda, Plested, Emma, Provstgaard-Morys, Samuel, Ramasamy, Maheshi, Robinson, Hannah, Sanders, Katherine, Smith, Andrew, Snape, Matthew D., Song, Rinn, Sutherland, Rebecca K., Thomson, Emma C., Toshner, Mark, Turner, David P. J., Voysey, Merryn, and Williams, Christopher J.
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COVID-19 Vaccines ,SARS-CoV-2 ,Immunogenicity ,T cell ,Vaccination ,T-cell receptor ,Receptors, Antigen, T-Cell ,COVID-19 ,Biology ,Peripheral blood mononuclear cell ,Article ,T cell mediated immunity ,medicine.anatomical_structure ,ChAdOx1 nCoV-19 ,Spike Glycoprotein, Coronavirus ,Immunology ,medicine ,Humans ,Receptor ,CD8 - Abstract
AZD1222 (ChAdOx1 nCoV-19), a replication-deficient simian adenovirus-vectored vaccine, has demonstrated safety, efficacy, and immunogenicity against coronavirus disease 2019 (COVID-19) in clinical trials and real-world studies. We characterized CD4+ and CD8+ T-cell responses induced by AZD1222 vaccination in peripheral blood mononuclear cells (PBMCs) from 280 unique vaccine recipients aged 18–85 years who enrolled in the phase 2/3 COV002 trial. Total spike-specific CD4+ T cell helper type 1 (Th1) and CD8+ T-cell responses were significantly increased in AZD1222-vaccinated adults of all ages following two doses of AZD1222. CD4+ Th2 responses following AZD1222 vaccination were not detected. Furthermore, AZD1222-specific Th1 and CD8+ T cells both displayed a high degree of polyfunctionality in all adult age groups. T-cell receptor (TCR) β sequences from vaccinated participants mapped against TCR sequences known to react to SARS-CoV-2 revealed substantial breadth and depth across the SARS-CoV-2 spike protein for the AZD1222-induced CD4+ and CD8+ T-cell responses. Overall, AZD1222 vaccination induced a robust, polyfunctional Th1-dominated T-cell response, with broad CD4+ and CD8+ T-cell coverage across the SARS-CoV-2 spike protein.One Sentence SummaryPolyfunctional CD4+ and CD8+ T-cell responses are elicited against the SARS-CoV-2 spike protein following vaccination with AZD1222
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- 2021
19. Efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 VOC 202012/01 (B.1.1.7), an exploratory analysis of a randomised controlled trial
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Emary, Katherine RW, Golubchik, Tanya, Aley, Parvinder K, Ariani, Cristina V, Angus, Brian, Bibi, Sagida, Blane, Beth, Bonsall, David, Cicconi, Paola, Charlton, Sue, Clutterbuck, Elizabeth A, Collins, Andrea M, Cox, Tony, Darton, Thomas C, Dold, Christina, Douglas, Alexander D, Duncan, Christopher JA, Ewer, Katie J, Flaxman, Amy L, Faust, Saul N, Ferreir, Daniela M, Feng, Shuo, Finn, Adam, Folegatti, Pedro M, Fuskova, Michelle, Galiza, Eva, Goodman, Anna L, Green, Catherine M, Green, Christopher A, Greenland, Melanie, Hallis, Bassam, Heath, Paul T, Hay, Jodie, Hill, Helen C, Jenkin, Daniel, Kerridge, Simon, Lazarus, Rajeka, Libri, Vincenzo, Lillie, Patrick J, Ludden, Catherine, Marchevsky, Natalie G, Minassian, Angela M, McGregor, Alastair C, Mujadidi, Yama F, Phillips, Daniel J, Plested, Emma, Pollock, Katrina M, Robinson, Hannah, Smith, Andrew, Song, Rinn, Snape, Matthew D, Sutherland, Rebecca K, Thomson, Emma C, Toshner, Mark, Turner, David PJ, Vekemans, Johan, Villafana, Tonya L, Williams, Christopher J, Hill, Adrian VS, Lambe, Teresa, Gilbert, Sarah C, Voysey, Merryn, Ramasamy, Maheshi N, Pollard, Andrew J, Consortium, The COVID-19 Genomics UK, Project, The AMPHEUS, Group, The Oxford COVID-19 Vaccine Trial, Toshner, Mark [0000-0002-3969-6143], and Apollo - University of Cambridge Repository
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A new variant of SARS-CoV-2, B.1.1.7, emerged as the dominant cause of COVID-19 disease in the United Kingdom from November 2020. Here we report efficacy of the adenoviral vector vaccine, ChAdOx1 nCoV-19, against this variant., COVID-19 Genomics UK is supported by funding from the Medical Research Council, part of UK Research and Innovation, the NIHR, and Genome Research, operating as the Wellcome Sanger Institute.
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- 2021
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20. Durability of ChAdOx1 nCov-19 (AZD1222) vaccination in people living with HIV - responses to SARS-CoV-2, variants of concern and circulating coronaviruses
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Ogbe, Ane, primary, Pace, Mathew, additional, Bittaye, Mustapha, additional, Tipoe, Timothy, additional, Adele, Sandra, additional, Alagaratnam, Jasmini, additional, Aley, Parvinder K, additional, Ansari, M. Azim, additional, Bara, Anna, additional, Broadhead, Samantha, additional, Brown, Anthony, additional, Brown, Helen, additional, Cappuccini, Federica, additional, Cinardo, Paola, additional, Dejnirattisai, Wanwisa, additional, Ewer, Katie J., additional, Fok, Henry, additional, Folegatti, Pedro M., additional, Fowler, Jamie, additional, Godfrey, Leila, additional, Goodman, Anna L., additional, Jackson, Bethany, additional, Jenkin, Daniel, additional, Jones, Mathew, additional, Longet, Stephanie, additional, Makinson, Rebecca, additional, Marchevsky, Natalie G., additional, Mathew, Moncy, additional, Mazzella, Andrea, additional, Mujadidi, Yama F., additional, Parolini, Lucia, additional, Petersen, Claire, additional, Plested, Emma, additional, Pollock, Katrina M., additional, Rajeswaran, Thurkka, additional, Ramasamy, Maheshi N., additional, Rhead, Sarah, additional, Robinson, Hannah, additional, Robinson, Nicola, additional, Sanders, Helen, additional, Serrano, Sonia, additional, Stockmann, Helen, additional, Tipton, Tom, additional, Waters, Anele, additional, Zacharopoulou, Panagiota, additional, Barnes, Eleanor, additional, Dunachie, Susanna, additional, Goulder, Philip, additional, Klenerman, Paul, additional, Screaton, Gavin R., additional, Winston, Alan, additional, Hill, Adrian V. S., additional, Gilbert, Sarah C., additional, Carroll, Miles, additional, Pollard, Andrew J, additional, Fidler, Sarah, additional, Fox, Julie, additional, Lambe, Teresa, additional, and Frater, John, additional
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- 2021
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21. Safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 in HIV infection: a single-arm substudy of a phase 2/3 clinical trial
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Frater, John, primary, Ewer, Katie J, additional, Ogbe, Ane, additional, Pace, Mathew, additional, Adele, Sandra, additional, Adland, Emily, additional, Alagaratnam, Jasmini, additional, Aley, Parvinder K, additional, Ali, Mohammad, additional, Ansari, M Azim, additional, Bara, Anna, additional, Bittaye, Mustapha, additional, Broadhead, Samantha, additional, Brown, Anthony, additional, Brown, Helen, additional, Cappuccini, Federica, additional, Cooney, Enya, additional, Dejnirattisai, Wanwisa, additional, Dold, Christina, additional, Fairhead, Cassandra, additional, Fok, Henry, additional, Folegatti, Pedro M, additional, Fowler, Jamie, additional, Gibbs, Charlotte, additional, Goodman, Anna L, additional, Jenkin, Daniel, additional, Jones, Mathew, additional, Makinson, Rebecca, additional, Marchevsky, Natalie G, additional, Mujadidi, Yama F, additional, Nguyen, Hanna, additional, Parolini, Lucia, additional, Petersen, Claire, additional, Plested, Emma, additional, Pollock, Katrina M, additional, Ramasamy, Maheshi N, additional, Rhead, Sarah, additional, Robinson, Hannah, additional, Robinson, Nicola, additional, Rongkard, Patpong, additional, Ryan, Fiona, additional, Serrano, Sonia, additional, Tipoe, Timothy, additional, Voysey, Merryn, additional, Waters, Anele, additional, Zacharopoulou, Panagiota, additional, Barnes, Eleanor, additional, Dunachie, Susanna, additional, Goulder, Philip, additional, Klenerman, Paul, additional, Screaton, Gavin R, additional, Winston, Alan, additional, Hill, Adrian V S, additional, Gilbert, Sarah C, additional, Pollard, Andrew J, additional, Fidler, Sarah, additional, Fox, Julie, additional, Lambe, Teresa, additional, Watson, Marion E.E., additional, Song, Rinn, additional, Cicconi, Paola, additional, Minassian, Angela M., additional, Bibi, Sagida, additional, Kerridge, Simon, additional, Singh, Nisha, additional, Green, Catherine M., additional, Douglas, Alexander D., additional, Lawrie, Alison M., additional, and Clutterbuck, Elizabeth A., additional
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22. Author Correction: Phase 1/2 trial of SARS-CoV-2 vaccine ChAdOx1 nCoV-19 with a booster dose induces multifunctional antibody responses
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Barrett, Jordan R., Belij-Rammerstorfer, Sandra, Dold, Christina, Ewer, Katie J., Folegatti, Pedro M., Gilbride, Ciaran, and Halkerston, Rachel
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Biological sciences ,Health - Abstract
A Correction to this paper has been published: https://doi.org/10.1038/s41591-021-01372-z., Author(s): Jordan R. Barrett [sup.1] , Sandra Belij-Rammerstorfer [sup.1] , Christina Dold [sup.2] , Katie J. Ewer [sup.1] , Pedro M. Folegatti [sup.1] , Ciaran Gilbride [sup.1] , Rachel Halkerston [...]
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- 2021
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23. Efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 variant of concern 202012/01 (B.1.1.7): an exploratory analysis of a randomised controlled trial
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Emary, Katherine RW, Golubchik, Tanya, Aley, Parvinder K, Ariani, Cristina V, Angus, Brian, Bibi, Sagida, Blane, Beth, Bonsall, David, Cicconi, Paola, Charlton, Sue, Clutterbuck, Elizabeth A, Collins, Andrea M, Cox, Tony, Darton, Thomas C, Dold, Christina, Douglas, Alexander D, Duncan, Christopher JA, Ewer, Katie J, Flaxman, Amy L, Faust, Saul N, Ferreira, Daniela M, Feng, Shuo, Finn, Adam, Folegatti, Pedro M, Fuskova, Michelle, Galiza, Eva, Goodman, Anna L, Green, Catherine M, Green, Christopher A, Greenland, Melanie, Hallis, Bassam, Heath, Paul T, Hay, Jodie, Hill, Helen C, Jenkin, Daniel, Kerridge, Simon, Lazarus, Rajeka, Libri, Vincenzo, Lillie, Patrick J, Ludden, Catherine, Marchevsky, Natalie G, Minassian, Angela M, McGregor, Alastair C, Mujadidi, Yama F, Phillips, Daniel J, Plested, Emma, Pollock, Katrina M, Robinson, Hannah, Smith, Andrew, Song, Rinn, Snape, Matthew D, Sutherland, Rebecca K, Thomson, Emma C, Toshner, Mark, Turner, David PJ, Vekemans, Johan, Villafana, Tonya L, Williams, Christopher J, Hill, Adrian VS, Lambe, Teresa, Gilbert, Sarah C, Voysey, Merryn, Ramasamy, Maheshi N, Pollard, Andrew J, COVID-19 Genomics UK Consortium, AMPHEUS Project, Oxford COVID-19 Vaccine Trial Group, Toshner, Mark [0000-0002-3969-6143], and Apollo - University of Cambridge Repository
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Adult ,Male ,COVID-19 Vaccines ,Adolescent ,SARS-CoV-2 ,COVID-19 ,Middle Aged ,Viral Load ,Antibodies, Neutralizing ,United Kingdom ,Young Adult ,COVID-19 Nucleic Acid Testing ,ChAdOx1 nCoV-19 ,Humans ,Female ,Single-Blind Method ,Nucleic Acid Amplification Techniques ,Pandemics - Abstract
BACKGROUND: A new variant of SARS-CoV-2, B.1.1.7, emerged as the dominant cause of COVID-19 disease in the UK from November, 2020. We report a post-hoc analysis of the efficacy of the adenoviral vector vaccine, ChAdOx1 nCoV-19 (AZD1222), against this variant. METHODS: Volunteers (aged ≥18 years) who were enrolled in phase 2/3 vaccine efficacy studies in the UK, and who were randomly assigned (1:1) to receive ChAdOx1 nCoV-19 or a meningococcal conjugate control (MenACWY) vaccine, provided upper airway swabs on a weekly basis and also if they developed symptoms of COVID-19 disease (a cough, a fever of 37·8°C or higher, shortness of breath, anosmia, or ageusia). Swabs were tested by nucleic acid amplification test (NAAT) for SARS-CoV-2 and positive samples were sequenced through the COVID-19 Genomics UK consortium. Neutralising antibody responses were measured using a live-virus microneutralisation assay against the B.1.1.7 lineage and a canonical non-B.1.1.7 lineage (Victoria). The efficacy analysis included symptomatic COVID-19 in seronegative participants with a NAAT positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to vaccine received. Vaccine efficacy was calculated as 1 - relative risk (ChAdOx1 nCoV-19 vs MenACWY groups) derived from a robust Poisson regression model. This study is continuing and is registered with ClinicalTrials.gov, NCT04400838, and ISRCTN, 15281137. FINDINGS: Participants in efficacy cohorts were recruited between May 31 and Nov 13, 2020, and received booster doses between Aug 3 and Dec 30, 2020. Of 8534 participants in the primary efficacy cohort, 6636 (78%) were aged 18-55 years and 5065 (59%) were female. Between Oct 1, 2020, and Jan 14, 2021, 520 participants developed SARS-CoV-2 infection. 1466 NAAT positive nose and throat swabs were collected from these participants during the trial. Of these, 401 swabs from 311 participants were successfully sequenced. Laboratory virus neutralisation activity by vaccine-induced antibodies was lower against the B.1.1.7 variant than against the Victoria lineage (geometric mean ratio 8·9, 95% CI 7·2-11·0). Clinical vaccine efficacy against symptomatic NAAT positive infection was 70·4% (95% CI 43·6-84·5) for B.1.1.7 and 81·5% (67·9-89·4) for non-B.1.1.7 lineages. INTERPRETATION: ChAdOx1 nCoV-19 showed reduced neutralisation activity against the B.1.1.7 variant compared with a non-B.1.1.7 variant in vitro, but the vaccine showed efficacy against the B.1.1.7 variant of SARS-CoV-2. FUNDING: UK Research and Innovation, National Institute for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midlands NIHR Clinical Research Network, and AstraZeneca.
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- 2021
24. Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials
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Voysey, Merryn, Costa Clemens, Sue Ann, Madhi, Shabir A, Weckx, Lily Y, Folegatti, Pedro M, Aley, Parvinder K, Angus, Brian, Baillie, Vicky L, Barnabas, Shaun L, Bhorat, Qasim E, Bibi, Sagida, Briner, Carmen, Cicconi, Paola, Clutterbuck, Elizabeth A, Collins, Andrea M, Cutland, Clare L, Darton, Thomas C, Dheda, Keertan, Dold, Christina, Duncan, Christopher JA, Emary, Katherine RW, Ewer, Katie J, Flaxman, Amy, Fairlie, Lee, Faust, Saul N, Feng, Shuo, Ferreira, Daniela M, Finn, Adam, Galiza, Eva, Goodman, Anna L, Green, Catherine M, Green, Christopher A, Greenland, Melanie, Hill, Catherine, Hill, Helen C, Hirsch, Ian, Izu, Alane, Jenkin, Daniel, Joe, Carina CD, Kerridge, Simon, Koen, Anthonet, Kwatra, Gaurav, Lazarus, Rajeka, Libri, Vincenzo, Lillie, Patrick J, Marchevsky, Natalie G, Marshall, Richard P, Mendes, Ana VA, Milan, Eveline P, Minassian, Angela M, McGregor, Alastair, Mujadidi, Yama F, Nana, Anusha, Padayachee, Sherman D, Phillips, Daniel J, Pittella, Ana, Plested, Emma, Pollock, Katrina M, Ramasamy, Maheshi N, Ritchie, Adam J, Robinson, Hannah, Schwarzbold, Alexandre V, Smith, Andrew, Song, Rinn, Snape, Matthew D, Sprinz, Eduardo, Sutherland, Rebecca K, Thomson, Emma C, Török, M Estée, Toshner, Mark, Turner, David PJ, Vekemans, Johan, Villafana, Tonya L, White, Thomas, Williams, Christopher J, Douglas, Alexander D, Hill, Adrian VS, Lambe, Teresa, Gilbert, Sarah C, Pollard, Andrew J, and Oxford COVID Vaccine Trial Group
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Background\ud The ChAdOx1 nCoV-19 (AZD1222) vaccine has been approved for emergency use by the UK regulatory authority, Medicines and Healthcare products Regulatory Agency, with a regimen of two standard doses given with an interval of 4-12 weeks. The planned roll-out in the UK will involve vaccinating people in high-risk categories with their first dose immediately, and delivering the second dose 12 weeks later. Here, we provide both a further prespecified pooled analysis of trials of ChAdOx1 nCoV-19 and exploratory analyses of the impact on immunogenicity and efficacy of extending the interval between priming and booster doses. In addition, we show the immunogenicity and protection afforded by the first dose, before a booster dose has been offered.MethodsWe present data from three single-blind randomised controlled trials-one phase 1/2 study in the UK (COV001), one phase 2/3 study in the UK (COV002), and a phase 3 study in Brazil (COV003)-and one double-blind phase 1/2 study in South Africa (COV005). As previously described, individuals 18 years and older were randomly assigned 1:1 to receive two standard doses of ChAdOx1 nCoV-19 (5 × 1010 viral particles) or a control vaccine or saline placebo. In the UK trial, a subset of participants received a lower dose (2·2 × 1010 viral particles) of the ChAdOx1 nCoV-19 for the first dose. The primary outcome was virologically confirmed symptomatic COVID-19 disease, defined as a nucleic acid amplification test (NAAT)-positive swab combined with at least one qualifying symptom (fever ≥37·8°C, cough, shortness of breath, or anosmia or ageusia) more than 14 days after the second dose. Secondary efficacy analyses included cases occuring at least 22 days after the first dose. Antibody responses measured by immunoassay and by pseudovirus neutralisation were exploratory outcomes. All cases of COVID-19 with a NAAT-positive swab were adjudicated for inclusion in the analysis by a masked independent endpoint review committee. The primary analysis included all participants who were SARS-CoV-2 N protein seronegative at baseline, had had at least 14 days of follow-up after the second dose, and had no evidence of previous SARS-CoV-2 infection from NAAT swabs. Safety was assessed in all participants who received at least one dose. The four trials are registered at ISRCTN89951424 (COV003) and ClinicalTrials.gov, NCT04324606 (COV001), NCT04400838 (COV002), and NCT04444674 (COV005).FindingsBetween April 23 and Dec 6, 2020, 24 422 participants were recruited and vaccinated across the four studies, of whom 17 178 were included in the primary analysis (8597 receiving ChAdOx1 nCoV-19 and 8581 receiving control vaccine). The data cutoff for these analyses was Dec 7, 2020. 332 NAAT-positive infections met the primary endpoint of symptomatic infection more than 14 days after the second dose. Overall vaccine efficacy more than 14 days after the second dose was 66·7% (95% CI 57·4-74·0), with 84 (1·0%) cases in the 8597 participants in the ChAdOx1 nCoV-19 group and 248 (2·9%) in the 8581 participants in the control group. There were no hospital admissions for COVID-19 in the ChAdOx1 nCoV-19 group after the initial 21-day exclusion period, and 15 in the control group. 108 (0·9%) of 12 282 participants in the ChAdOx1 nCoV-19 group and 127 (1·1%) of 11 962 participants in the control group had serious adverse events. There were seven deaths considered unrelated to vaccination (two in the ChAdOx1 nCov-19 group and five in the control group), including one COVID-19-related death in one participant in the control group. Exploratory analyses showed that vaccine efficacy after a single standard dose of vaccine from day 22 to day 90 after vaccination was 76·0% (59·3-85·9). Our modelling analysis indicated that protection did not wane during this initial 3-month period. Similarly, antibody levels were maintained during this period with minimal waning by day 90 (geometric mean ratio [GMR] 0·66 [95% CI 0·59-0·74]). In the participants who received two standard doses, after the second dose, efficacy was higher in those with a longer prime-boost interval (vaccine efficacy 81·3% [95% CI 60·3-91·2] at ≥12 weeks) than in those with a short interval (vaccine efficacy 55·1% [33·0-69·9] at InterpretationThe results of this primary analysis of two doses of ChAdOx1 nCoV-19 were consistent with those seen in the interim analysis of the trials and confirm that the vaccine is efficacious, with results varying by dose interval in exploratory analyses. A 3-month dose interval might have advantages over a programme with a short dose interval for roll-out of a pandemic vaccine to protect the largest number of individuals in the population as early as possible when supplies are scarce, while also improving protection after receiving a second dose.FundingUK Research and Innovation, National Institutes of Health Research (NIHR), The Coalition for Epidemic Preparedness Innovations, the Bill & Melinda Gates Foundation, the Lemann Foundation, Rede D'Or, the Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca.
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- 2021
25. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK
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Voysey, Merryn, Clemens, Sue Ann Costa, Madhi, Shabir A., Weckx, Lily Y., Folegatti, Pedro M., Aley, Parvinder K., Angus, Brian, Baillie, Vicky L., Barnabas, Shaun L., Bhorat, Qasim E., Bibi, Sagida, Briner, Carmen, Cicconi, Paola, Collins, Andrea M., Colin-Jones, Rachel, Cutland, Clare L., Darton, Thomas C., Dheda, Keertan, Duncan, Christopher J. A., Emary, Katherine R. W., Ewer, Katie J., Fairlie, Lee, Faust, Saul N., Feng, Shuo, Ferreira, Daniela M., Finn, Adam, Goodman, Anna L., Green, Catherine M., Green, Christopher A., Heath, Paul T., Hill, Catherine, Hill, Helen, Hirsch, Ian, Hodgson, Susanne H. C., Izu, Alane, Jackson, Susan, Jenkin, Daniel, Joe, Carina C. D., Kerridge, Simon, Koen, Anthonet, Kwatra, Gaurav, Lazarus, Rajeka, Lawrie, Alison M., Lelliott, Alice, Libri, Vincenzo, Lillie, Patrick J., Mallory, Raburn, Mendes, Ana V. A., Milan, Eveline P., Minassian, Angela M., McGregor, Alastair, Morrison, Hazel, Mujadidi, Yama F., Nana, Anusha, O'Reilly, Peter J., Padayachee, Sherman D., Pittella, Ana, Plested, Emma, Pollock, Katrina M., Ramasamy, Maheshi N., Rhead, Sarah, Schwarzbold, Alexandre V., Singh, Nisha, Smith, Andrew, Song, Rinn, Snape, Matthew D., Sprinz, Eduardo, Sutherland, Rebecca K., Tarrant, Richard, Thomson, Emma C., Török, Mark and Turner, Sorio, Guilherme L., Sorley, Kim, Sosa-Rodriguez, Tiffany, Souza, Cinthia M.C.D.L., Souza, Bruno S.D.F., Souza, Alessandra R., Spencer, Alexandra J., Spina, Fernanda, Spoors, Louise, Stafford, Lizzie, Stamford, Imogen, Starinskij, Igor, Stein, Ricardo, Steven, Jill, Stockdale, Lisa, Stockwell, Lisa V., Strickland, Louise H., Stuart, Arabella C., Sturdy, Ann, Sutton, Natalina, Szigeti, Anna, Tahiri-Alaoui, Abdessamad, Tanner, Rachel, Taoushanis, Carol, Tarr, Alexander W., Taylor, Keja, Taylor, Ursula, Taylor, Iona Jennifer, Taylor, Justin, te Water Naude, Rebecca, Themistocleous, Yrene, Themistocleous, Andreas, Thomas, Merin, Thomas, Kelly, Thomas, Tonia M., Thombrayil, Asha, Thompson, Fawziyah, Thompson, Amber, Thompson, Kevin, Thompson, Ameeka, Thomson, Julia, Thornton-Jones, Viv, Tighe, Patrick J., Tinoco, Lygia Accioly, Tiongson, Gerlynn, Tladinyane, Bonolo, Tomasicchio, Michele, Tomic, Adriana, Tonks, Susan, Tran, Nguyen, Tree, Julia, Trillana, Gerry, Trinham, Charlotte, Trivett, Rose, Truby, Adam, Tsheko, Betty Lebogang, Turabi, Aadil, Turner, Richard, Turner, Cheryl, Ulaszewska, Marta, Underwood, Benjamin R., Varughese, Rachel, Verbart, Dennis, Verheul, Marije, Vichos, Iason, Vieira, Taiane, Waddington, Claire S., Walker, Laura, Wallis, Erica, Wand, Matthew, Warbick, Deborah, Wardell, Theresa, Warimwe, George, Warren, Sarah C., Watkins, Bridget, Watson, Ekaterina, Webb, Stewart, Webb-Bridges, Alice, Webster, Angela, Welch, Jessica, Wells, Jeanette, West, Alison, White, Caroline, White, Rachel, Williams, Paul, Williams, Rachel L., Winslow, Rebecca, Woodyer, Mark, Worth, Andrew T., Wright, Danny, Wroblewska, Marzena, Yao, Andy, Zimmer, Rafael, Zizi, Dalila, and Zuidewind, Peter
- Abstract
Background: \ud A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials.\ud \ud Methods: \ud This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674.\ud \ud Findings: \ud Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation.\ud \ud Interpretation: \ud ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials.\ud \ud Funding: \ud UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D’Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca.
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- 2021
26. Efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 lineages circulating in Brazil
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Clemens, Sue Ann Costa, Folegatti, Pedro M., Emary, Katherine R. W., Weckx, Lily Yin, Ratcliff, Jeremy, Bibi, Sagida, Sprinz, Eduardo, Pollard, Andrew J., and Oxford COVID Vaccine Trial Group
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Carga viral ,Doenças transmissíveis ,Vaccines ,SARS-CoV-2 ,Viral infection ,Vacinas contra COVID-19 ,COVID-19 ,Infectious diseases - Abstract
Several COVID-19 vaccines have shown good efficacy in clinical trials, but there remains uncertainty about the efficacy of vaccines against different variants. Here, we investigate the efficacy of ChAdOx1 nCoV-19 (AZD1222) against symptomatic COVID-19 in a post-hoc exploratory analysis of a Phase 3 randomised trial in Brazil (trial registration ISRCTN89951424). Nose and throat swabs were tested by PCR in symptomatic participants. Sequencing and genotyping of swabs were performed to determine the lineages of SARS-CoV-2 circulating during the study. Protection against any symptomatic COVID-19 caused by the Zeta (P.2) variant was assessed in 153 cases with vaccine efficacy (VE) of 69% (95% CI 55, 78). 49 cases of B.1.1.28 occurred and VE was 73% (46, 86). The Gamma (P.1) variant arose later in the trial and fewer cases (N = 18) were available for analysis. VE was 64% (−2, 87). ChAdOx1 nCoV-19 provided 95% protection (95% CI 61%, 99%) against hospitalisation due to COVID-19. In summary, we report that ChAdOx1 nCoV-19 protects against emerging variants in Brazil despite the presence of the spike protein mutation E484K.
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- 2021
27. T cell and antibody responses induced by a single dose of ChAdOx1 nCoV-19 (AZD1222) vaccine in a phase 1/2 clinical trial
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Ewer, Katie J., Barrett, Jordan R., Belij-Rammerstorfer, Sandra, Sharpe, Hannah, Makinson, Rebecca, Morter, Richard, Flaxman, Amy, Wright, Daniel, Bellamy, Duncan, Bittaye, Mustapha, Dold, Christina, Provine, Nicholas M., Aboagye, Jeremy, Fowler, Jamie, Silk, Sarah E., Alderson, Jennifer, Aley, Parvinder K., Angus, Brian, Berrie, Eleanor, Bibi, Sagida, Cicconi, Paola, Clutterbuck, Elizabeth A., Chelysheva, Irina, Folegatti, Pedro M., Fuskova, Michelle, Green, Catherine M., Jenkin, Daniel, Kerridge, Simon, Lawrie, Alison, Minassian, Angela M., Moore, Maria, Mujadidi, Yama, Plested, Emma, Poulton, Ian, Ramasamy, Maheshi N., Robinson, Hannah, Song, Rinn, Snape, Matthew D., Tarrant, Richard, Voysey, Merryn, Watson, Marion E. E., Douglas, Alexander D., Hill, Adrian V. S., Gilbert, Sarah C., Pollard, Andrew J., Lambe, Teresa, Ali, Aabidah, Allen, Elizabeth, Baker, Megan, Barnes, Eleanor, Borthwick, Nicola, Boyd, Amy, Brown-O’Sullivan, Charlie, Burgoyne, Joshua, Byard, Nicholas, Puig, Ingrid Cabrera, Cappuccini, Federica, Cho, Jee-Sun, Clark, Elizabeth, Crocker, Wendy E. M., Datoo, Mehreen S., Davies, Hannah, Donnellan, Francesca R., Dunachie, Susanna Jane, Edwards, Nick J., Elias, Sean C., Furze, Julie, Gilbride, Ciaran, Gorini, Giacomo, Gupta, Gaurav, Harris, Stephanie A., Hodgson, Susanne H. C., Hou, Mimi M., Jackson, Susan, Jones, Kathryn, Kailath, Reshma, King, Lloyd, Larkworthy, Colin W., Li, Yuanyuan, Lias, Amelia M., Linder, Aline, Lipworth, Samuel, Ramon, Raquel Lopez, Madhavan, Meera, Marlow, Emma, Marshall, Julia L., Mentzer, Alexander J., Morrison, Hazel, Moya, Nathifa, Mukhopadhyay, Ekta, Noé, Andrés, Nugent, Fay L., Pipini, Dimitra, Pulido-Gomez, David, Lopez, Fernando Ramos, Ritchie, Adam John, Rudiansyah, Indra, Salvador, Stephannie, Sanders, Helen, Satti, Iman, Shea, Adam, Silk, Sarah, Spencer, Alexandra J., Tanner, Rachel, Taylor, Iona Jennifer, Themistocleous, Yrene, Thomas, Merin, Tran, Nguyen, Truby, Adam, Turner, Cheryl, Turner, Nicola, Ulaszewska, Marta, Worth, Andrew T., Kingham-Page, Lucy, Alvarez, Marco Polo Peralta, Anslow, Rachel, Bates, Louise, Beadon, Kirsten, Beckley, Rebecca, Beveridge, Amy, Bijker, Else Margreet, Blackwell, Luke, Burbage, Jamie, Camara, Susana, Carr, Melanie, Colin-Jones, Rachel, Cooper, Rachel, Cunningham, Christina J., Demissie, Tesfaye, Maso, Claudio Di, Douglas, Naomi, Drake-Brockman, Rachael, Drury, Ruth Elizabeth, Emary, Katherine R. W., Felle, Sally, Feng, Shuo, Silva, Carla Ferreira Da, Ford, Karen J., Francis, Emma, Gracie, Lara, Hamlyn, Joseph, Hanumunthadu, Brama, Harrison, Daisy, Hart, Thomas C., Hawkins, Sophia, Hill, Jennifer, Howe, Elizabeth, Howell, Nicola, Jones, Elizabeth, Keen, Jade, Kelly, Sarah, Kerr, David, Khan, Liaquat, Kinch, Jasmin, Koleva, Stanislava, Lees, Emily A., Lelliott, Alice, Liu, Xinxue, Marchevsky, Natalie G., Marinou, Spyridoula, McEwan, Joanne, Morey, Ella, Morshead, Gertraud, Muller, Jilly, Munro, Claire, Murphy, Sarah, Mweu, Philomena, Nuthall, Elizabeth, O’Brien, Katie, O’Connor, Daniel, O’Reilly, Peter John, Oguti, Blanché, Osborne, Piper, Owino, Nelly, Parker, Kaye, Pfafferott, Katja, Phillips, Daniel, Provstgaard-Morys, Samuel, Ratcliffe, Helen, Rawlinson, Thomas, Rhead, Sarah, Roberts, Hannah, Sanders, Katherine, Silva-Reyes, Laura, Rollier, Christine S., Smith, Catherine C., Smith, David J., Stockdale, Lisa, Szigeti, Anna, Thomas, Tonia M., Thompson, Amber, Tomic, Adriana, Tonks, Susan, Varughese, Rachel, Verheul, Marije K., Vichos, Iason, Walker, Laura, White, Caroline, White, Rachel, Yao, Xin Li, Conlon, Christopher P., Frater, John, Cifuentes, Liliana, Baleanu, Ioana, Bolam, Emma, Boland, Elena, Brenner, Tanja, Damratoski, Brad E., Datta, Chandra, Muhanna, Omar El, Fisher, Richard, Galian-Rubio, Pablo, Hodges, Gina, Jackson, Frederic, Liu, Shuchang, Loew, Lisa, Morgans, Roisin, Morris, Susan Jane, Olchawski, Vicki, Oliveria, Catarina, Parracho, Helena, Pabon, Emilia Reyes, Tahiri-Alaoui, Abdessamad, Taylor, Keja, Williams, Paul, Zizi, Dalila, Arbe-Barnes, Edward H., Baker, Philip, Batten, Alexander, Downing, Charlotte, Drake, Jonathan, English, Marcus Rex, Henry, John Aaron, Iveson, Poppy, Killen, Annabel, King, Thomas B., Larwood, Jessica P. J., Mallett, Garry, Mansatta, Kushal, Mirtorabi, Neginsadat, Patrick-Smith, Maia, Perring, James, Radia, Kajal, Roche, Sophie, Schofield, Ella, Naude, Rebecca te Water, Towner, James, Baker, Natalie, Bewley, Kevin R., Brunt, Emily, Buttigieg, Karen R., Carroll, Miles W., Charlton, Sue, Coombes, Naomi S., Elmore, Michael J., Godwin, Kerry, Hallis, Bassam, Knott, Daniel, McInroy, Lorna, Shaik, Imam, Thomas, Kelly, Tree, Julia A., Blundell, Caitlin L., Cao, Michelangelo, Kelly, Dearbhla, Schmid, Annina, Skelly, Donal T., Themistocleous, Andreas, Dong, Tao, Field, Samantha, Hamilton, Elizabeth, Kelly, Elizabeth, Klenerman, Paul, Knight, Julian C., Lie, Yolanda, Petropoulos, Christos, Sedik, Cynthia, Wrin, Terri, Meddaugh, Gretchen, Peng, Yanchun, Screaton, Gavin, and Stafford, Elizabeth
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0301 basic medicine ,biology ,business.industry ,T cell ,Immunogenicity ,General Medicine ,Vaccine efficacy ,General Biochemistry, Genetics and Molecular Biology ,Vaccination ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Immune system ,Immunity ,030220 oncology & carcinogenesis ,Immunology ,biology.protein ,medicine ,Cytotoxic T cell ,Antibody ,business - Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus Disease 2019 (COVID-19), has caused a global pandemic, and safe, effective vaccines are urgently needed1. Strong, Th1-skewed T cell responses can drive protective humoral and cell-mediated immune responses2 and might reduce the potential for disease enhancement3. Cytotoxic T cells clear virus-infected host cells and contribute to control of infection4. Studies of patients infected with SARS-CoV-2 have suggested a protective role for both humoral and cell-mediated immune responses in recovery from COVID-19 (refs. 5,6). ChAdOx1 nCoV-19 (AZD1222) is a candidate SARS-CoV-2 vaccine comprising a replication-deficient simian adenovirus expressing full-length SARS-CoV-2 spike protein. We recently reported preliminary safety and immunogenicity data from a phase 1/2 trial of the ChAdOx1 nCoV-19 vaccine (NCT04400838)7 given as either a one- or two-dose regimen. The vaccine was tolerated, with induction of neutralizing antibodies and antigen-specific T cells against the SARS-CoV-2 spike protein. Here we describe, in detail, exploratory analyses of the immune responses in adults, aged 18–55 years, up to 8 weeks after vaccination with a single dose of ChAdOx1 nCoV-19 in this trial, demonstrating an induction of a Th1-biased response characterized by interferon-γ and tumor necrosis factor-α cytokine secretion by CD4+ T cells and antibody production predominantly of IgG1 and IgG3 subclasses. CD8+ T cells, of monofunctional, polyfunctional and cytotoxic phenotypes, were also induced. Taken together, these results suggest a favorable immune profile induced by ChAdOx1 nCoV-19 vaccine, supporting the progression of this vaccine candidate to ongoing phase 2/3 trials to assess vaccine efficacy. A single dose of the ChAdOx1 nCoV-19 vaccine elicits antibodies and cytokine-producing T cells that might help control or prevent SARS-CoV-2 infection.
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- 2020
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28. Safety and Immunogenicity of Adenovirus and Poxvirus Vectored Vaccines against a Mycobacterium Avium Complex Subspecies
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Folegatti, Pedro M., primary, Flaxman, Amy, additional, Jenkin, Daniel, additional, Makinson, Rebecca, additional, Kingham-Page, Lucy, additional, Bellamy, Duncan, additional, Ramos Lopez, Fernando, additional, Sheridan, Jonathan, additional, Poulton, Ian, additional, Aboagye, Jeremy, additional, Tran, Nguyen, additional, Mitton, Celia, additional, Roberts, Rachel, additional, Lawrie, Alison M., additional, Hill, Adrian V. S., additional, Ewer, Katie J., additional, and Gilbert, Sarah, additional
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- 2021
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29. Tolerability and Immunogenicity After a Late Second Dose or a Third Dose of ChAdOx1 nCoV-19 (AZD1222)
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Flaxman, Amy, primary, Marchevsky, Natalie, additional, Jenkin, Daniel, additional, Aboagye, Jeremy, additional, Aley, Parvinder K., additional, Angus, Brian John, additional, Belij-Rammerstorfer, Sandra, additional, Bibi, Sagida, additional, Bittaye, Mustapha, additional, Cappuccini, Federica, additional, Cicconi, Paola, additional, Clutterbuck, Elizabeth, additional, Davies, Sophie, additional, Dejnirattisai, Wanwisa, additional, Dold, Christina, additional, Ewer, Katie, additional, Folegatti, Pedro M., additional, Fowler, Jamie, additional, Hill, Adrian V. S., additional, Kerridge, Simon, additional, Minassian, Angela M., additional, Mongkolspaya, Juthathip, additional, Farooq Mujadidi, Yama, additional, Plested, Emma, additional, Ramasamy, Maheshi N., additional, Robinson, Hannah, additional, Sanders, Helen, additional, Sheehan, Emma, additional, Smith, Holly, additional, Snape, Matthew D., additional, Song, Rinn, additional, Woods, Danielle, additional, Screaton, Gavin R., additional, Gilbert, Sarah C., additional, Voysey, Merryn, additional, Pollard, Andrew, additional, Lambe, Teresa, additional, and Group, The Oxford COVID Vaccine, additional
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- 2021
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30. Safety and Immunogenicity of the ChAdox1 nCoV-19 (AZD1222) Vaccine Against SARS-CoV-2 in HIV Infection
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Frater, John, primary, Ewer, Katie, additional, Ogbe, Ane, additional, Pace, Matthew, additional, Adele, Sandra, additional, Adland, Emily, additional, Alagaratnam, Jasmini, additional, Aley, Parvinder K., additional, Ali, Mohammad, additional, Ansari, M. Azim, additional, Bara, Anna, additional, Bittaye, Mustapha, additional, Broadhead, Sam, additional, Brown, Anthony, additional, Brown, Helen, additional, Cappuccini, Federica, additional, Cooney, Enya, additional, Dejnirattisai, Wanwisa, additional, Dold, Christina, additional, Fairhead, Cassandra, additional, Fok, Henry, additional, Folegatti, Pedro M., additional, Fowler, Jamie, additional, Gibbs, Charlotte, additional, Goodman, Anna L., additional, Jenkin, Daniel, additional, Jones, Mathew, additional, Makinson, Rebecca, additional, Marchevsky, Natalie G., additional, Farooq Mujadidi, Yama, additional, Nguyen, Hanna, additional, Parolini, Lucia, additional, Petersen, Claire, additional, Plested, Emma, additional, Pollock, Katrina M., additional, Ramasamy, Maheshi N., additional, Rhead, Sarah, additional, Robinson, Hannah, additional, Robinson, Nicola, additional, Rongkard, Patpong, additional, Ryan, Fiona, additional, Serrano, Sonia, additional, Stockmann, Helen, additional, Tipoe, Timothy, additional, Voysey, Merryn, additional, Waters, Anele, additional, Zacharopoulou, Panagiota, additional, Barnes, Eleanor, additional, Dunachie, Susanna, additional, Goulder, Philip, additional, Klenerman, Paul, additional, Screaton, Gavin, additional, Winston, Alan, additional, Hill, Adrian V. S., additional, Gilbert, Sarah C., additional, Pollard, Andrew, additional, Fidler, Sarah, additional, Fox, Julie, additional, Lambe, Teresa, additional, and Group, Oxford COVID Vaccine Trial, additional
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- 2021
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31. Efficacy of ChAdOx1 nCoV-19 (AZD1222) Vaccine Against SARS-CoV-2 VOC 202012/01 (B.1.1.7)
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Emary, Katherine R. W., primary, Golubchik, Tanya, additional, Aley, Parvinder K., additional, Ariani, Cristina V., additional, Angus, Brian John, additional, Bibi, Sagida, additional, Blane, Beth, additional, Bonsall, David, additional, Cicconi, Paola, additional, Charlton, Sue, additional, Clutterbuck, Elizabeth, additional, Collins, Andrea M., additional, Cox, Tony, additional, Darton, Thomas, additional, Dold, Christina, additional, Douglas, Alexander D., additional, Duncan, Christopher J. A., additional, Ewer, Katie, additional, Flaxman, Amy, additional, Faust, Saul N., additional, Ferreira, Daniela M., additional, Feng, Shuo, additional, Finn, Adam, additional, Folegatti, Pedro M., additional, Fuskova, Michelle, additional, Galiza, Eva, additional, Goodman, Anna L., additional, Green, Catherine M., additional, Green, Christopher A., additional, Greenland, Melanie, additional, Hallis, Bassam, additional, Heath, Paul T., additional, Hay, Jodie, additional, Hill, Helen C., additional, Jenkin, Daniel, additional, Kerridge, Simon, additional, Lazarus, Rajeka, additional, Libri, Vincenzo, additional, Lillie, Patrick J., additional, Ludden, Catherine, additional, Marchevsky, Natalie G., additional, Minassian, Angela M., additional, McGregor, Alastair C., additional, Farooq Mujadidi, Yama, additional, Phillips, Daniel J., additional, Plested, Emma, additional, Pollock, Katrina M., additional, Robinson, Hannah, additional, Smith, Andrew, additional, Song, Rinn, additional, Snape, Matthew D., additional, Sutherland, Rebecca K., additional, Thomson, Emma C., additional, Toshner, Mark, additional, Turner, David P. J., additional, Vekemans, Johan, additional, Villafana, Tonya L., additional, Williams, Christopher J., additional, Hill, Adrian V. S., additional, Lambe, Teresa, additional, Gilbert, Sarah C., additional, Voysey, Merryn, additional, Ramasamy, Maheshi N., additional, Pollard, Andrew, additional, and Group, Oxford COVID Vaccine Trial, additional
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- 2021
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32. Single Dose Administration, And The Influence Of The Timing Of The Booster Dose On Immunogenicity and Efficacy Of ChAdOx1 nCoV-19 (AZD1222) Vaccine
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Voysey, Merryn, primary, Costa Clemens, Sue Ann, additional, Madhi, Shabir A., additional, Weckx, Lily Yin, additional, Folegatti, Pedro M., additional, Aley, Parvinder K., additional, Angus, Brian John, additional, Baillie, Vicky, additional, Barnabas, Shaun L., additional, Bhorat, Qasim E., additional, Bibi, Sagida, additional, Briner, Carmen, additional, Cicconi, Paola, additional, Clutterbuck, Elizabeth, additional, Collins, Andrea M., additional, Cutland, Clare, additional, Darton, Thomas, additional, Dheda, Keertan, additional, Douglas, Alexander D., additional, Duncan, Christopher J. A., additional, Emary, Katherine R. W., additional, Ewer, Katie, additional, Flaxman, Amy, additional, Fairlie, Lee, additional, Faust, Saul N., additional, Feng, Shuo, additional, Ferreira, Daniela M., additional, Finn, Adam, additional, Galiza, Eva, additional, Goodman, Anna L., additional, Green, Catherine M., additional, Green, Christopher A., additional, Greenland, Melanie, additional, Hill, Catherine, additional, Hill, Helen C., additional, Hirsch, Ian, additional, Izu, Alane, additional, Jenkin, Daniel, additional, Kerridge, Simon, additional, Koen, Anthonet, additional, Kwatra, Gaurav, additional, Lazarus, Rajeka, additional, Libri, Vincenzo, additional, Lillie, Patrick J., additional, Marchevsky, Natalie G., additional, Marshall, Richard P., additional, Mendes, Ana Verena Almeida, additional, Milan, Eveline P., additional, Minassian, Angela M., additional, McGregor, Alastair C., additional, Farooq Mujadidi, Yama, additional, Nana, Anusha, additional, Payadachee, Sherman D., additional, Phillips, Daniel J., additional, Pittella, Ana, additional, Plested, Emma, additional, Pollock, Katrina M., additional, Ramasamy, Maheshi N., additional, Robinson, Hannah, additional, Schwarzbold, Alexandre V., additional, Smith, Andrew, additional, Song, Rinn, additional, Snape, Matthew D., additional, Sprinz, Eduardo, additional, Sutherland, Rebecca K., additional, Thomson, Emma C., additional, Torok, Mili, additional, Toshner, Mark, additional, Turner, David P. J., additional, Vekemans, Johan, additional, Villafana, Tonya L., additional, White, Thomas, additional, Williams, Christopher J., additional, Hill, Adrian V. S., additional, Lambe, Teresa, additional, Gilbert, Sarah C., additional, Pollard, Andrew, additional, and Group, Oxford COVID Vaccine Trial, additional
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- 2021
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33. Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial
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Ramasamy, Maheshi N, primary, Minassian, Angela M, additional, Ewer, Katie J, additional, Flaxman, Amy L, additional, Folegatti, Pedro M, additional, Owens, Daniel R, additional, Voysey, Merryn, additional, Aley, Parvinder K, additional, Angus, Brian, additional, Babbage, Gavin, additional, Belij-Rammerstorfer, Sandra, additional, Berry, Lisa, additional, Bibi, Sagida, additional, Bittaye, Mustapha, additional, Cathie, Katrina, additional, Chappell, Harry, additional, Charlton, Sue, additional, Cicconi, Paola, additional, Clutterbuck, Elizabeth A, additional, Colin-Jones, Rachel, additional, Dold, Christina, additional, Emary, Katherine R W, additional, Fedosyuk, Sofiya, additional, Fuskova, Michelle, additional, Gbesemete, Diane, additional, Green, Catherine, additional, Hallis, Bassam, additional, Hou, Mimi M, additional, Jenkin, Daniel, additional, Joe, Carina C D, additional, Kelly, Elizabeth J, additional, Kerridge, Simon, additional, Lawrie, Alison M, additional, Lelliott, Alice, additional, Lwin, May N, additional, Makinson, Rebecca, additional, Marchevsky, Natalie G, additional, Mujadidi, Yama, additional, Munro, Alasdair P S, additional, Pacurar, Mihaela, additional, Plested, Emma, additional, Rand, Jade, additional, Rawlinson, Thomas, additional, Rhead, Sarah, additional, Robinson, Hannah, additional, Ritchie, Adam J, additional, Ross-Russell, Amy L, additional, Saich, Stephen, additional, Singh, Nisha, additional, Smith, Catherine C, additional, Snape, Matthew D, additional, Song, Rinn, additional, Tarrant, Richard, additional, Themistocleous, Yrene, additional, Thomas, Kelly M, additional, Villafana, Tonya L, additional, Warren, Sarah C, additional, Watson, Marion E E, additional, Douglas, Alexander D, additional, Hill, Adrian V S, additional, Lambe, Teresa, additional, Gilbert, Sarah C, additional, Faust, Saul N, additional, Pollard, Andrew J, additional, Aboagye, Jeremy, additional, Adams, Kelly, additional, Ali, Aabidah, additional, Allen, Elizabeth R., additional, Allen, Lauren, additional, Allison, Jennifer L., additional, Andritsou, Foteini, additional, Anslow, Rachel, additional, Arbe-Barnes, Edward H., additional, Baker, Megan, additional, Baker, Natalie, additional, Baker, Philip, additional, Baleanu, Ioana, additional, Barker, Debbie, additional, Barnes, Eleanor, additional, Barrett, Jordan R., additional, Barrett, Kelly, additional, Bates, Louise, additional, Batten, Alexander, additional, Beadon, Kirsten, additional, Beckley, Rebecca, additional, Bellamy, Duncan, additional, Berg, Adam, additional, Bermejo, Laura, additional, Berrie, Eleanor, additional, Beveridge, Amy, additional, Bewley, Kevin, additional, Bijker, Else M., additional, Birch, Geeta, additional, Blackwell, Luke, additional, Bletchly, Heather, additional, Blundell, Caitlin L., additional, Blundell, Susannah R., additional, Bolam, Emma, additional, Boland, Elena, additional, Bormans, Daan, additional, Borthwick, Nicola, additional, Boukas, Konstantinos, additional, Bower, Thomas, additional, Bowring, Francesca, additional, Boyd, Amy, additional, Brenner, Tanja, additional, Brown, Phillip, additional, Brown-O'Sullivan, Charlie, additional, Bruce, Scott, additional, Brunt, Emily, additional, Burbage, Jamie, additional, Burgoyne, Joshua, additional, Buttigieg, Karen R., additional, Byard, Nicholas, additional, Cabera Puig, Ingrid, additional, Camara, Susana, additional, Cao, Michelangelo, additional, Cappuccini, Federica, additional, Carr, Melanie, additional, Carroll, Miles W., additional, Cashen, Paul, additional, Cavey, Ana, additional, Chadwick, Jim, additional, Challis, Ruth, additional, Chapman, David, additional, Charles, David, additional, Chelysheva, Irina, additional, Cho, Jee-Sun, additional, Cifuentes, Liliana, additional, Clark, Elizabeth, additional, Collins, Sarah, additional, Conlon, Christopher P., additional, Coombes, Naomi S., additional, Cooper, Rachel, additional, Cooper, Cushla, additional, Crocker, Wendy E.M., additional, Crosbie, Sarah, additional, Cullen, Dan, additional, Cunningham, Christina, additional, Cuthbertson, Fiona, additional, Datoo, Brad E., additional, Dando, Lynne, additional, Datoo, Mehreen S., additional, Datta, Chandrabali, additional, Davies, Hannah, additional, Davies, Sarah, additional, Davis, Elizabeth J., additional, Davis, Judith, additional, Dearlove, David, additional, Demissie, Tesfaye, additional, Di Marco, Stefania, additional, Di Maso, Claudio, additional, DiTirro, Danielle, additional, Docksey, Claire, additional, Dong, Tao, additional, Donnellan, Francesca R., additional, Douglas, Naomi, additional, Downing, Charlotte, additional, Drake, Jonathan, additional, Drake-Brockman, Rachael, additional, Drury, Ruth E., additional, Dunachie, Susanna J., additional, Edwards, Christopher J., additional, Edwards, Nick J., additional, El Muhanna, Omar, additional, Elias, Sean C., additional, Elliott, Ryan S., additional, Elmore, Michael J., additional, English, Marcus Rex, additional, Felle, Sally, additional, Feng, Shuo, additional, Ferreira Da Silva, Carla, additional, Field, Samantha, additional, Fisher, Richard, additional, Fixmer, Carine, additional, Ford, Karen J., additional, Fowler, Jamie, additional, Francis, Emma, additional, Frater, John, additional, Furze, Julie, additional, Galian-Rubio, Pablo, additional, Galloway, Celine, additional, Garlant, Harriet, additional, Gavrila, Madita, additional, Gibbons, Felicity, additional, Gibbons, Karyna, additional, Gilbride, Ciaran, additional, Gill, Hardeep, additional, Godwin, Kerry, additional, Gordon-Quayle, Katherine, additional, Gorini, Giacomo, additional, Goulston, Lyndsey, additional, Grabau, Caroline, additional, Gracie, Lara, additional, Graham, Nichola, additional, Greenwood, Nicola, additional, Griffiths, Oliver, additional, Gupta, Gaurav, additional, Hamilton, Elizabeth, additional, Hanumunthadu, Brama, additional, Harris, Stephanie A., additional, Harris, Tara, additional, Harrison, Daisy, additional, Hart, Thomas C., additional, Hartnell, Birgit, additional, Haskell, Louise, additional, Hawkins, Sophia, additional, Henry, John Aaron, additional, Hermosin Herrera, Macarena, additional, Hill, David, additional, Hill, Jennifer, additional, Hodges, Gina, additional, Hodgson, Susanne H.C., additional, Horton, Katie L., additional, Howe, Elizabeth, additional, Howell, Nicola, additional, Howes, Jessica, additional, Huang, Ben, additional, Humphreys, Jonathan, additional, Humphries, Holly E., additional, Iveson, Poppy, additional, Jackson, Frederic, additional, Jackson, Susan, additional, Jauregui, Sam, additional, Jeffers, Helen, additional, Jones, Bryony, additional, Jones, Christine E., additional, Jones, Elizabeth, additional, Jones, Kathryn, additional, Joshi, Amar, additional, Kailath, Reshma, additional, Keen, Jade, additional, Kelly, Dearbhla M., additional, Kelly, Sarah, additional, Kelly, Debbie, additional, Kerr, David, additional, Khan, Liaquat, additional, Khozoee, Baktash, additional, Killen, Annabel, additional, Kinch, Jasmin, additional, King, Lloyd D.W., additional, King, Thomas B., additional, Kingham, Lucy, additional, Klenerman, Paul, additional, Knight, Julian C., additional, Knott, Daniel, additional, Koleva, Stanislava, additional, Lang, Gail, additional, Larkworthy, Colin W., additional, Larwood, Jessica P.J., additional, Law, Rebecca, additional, Lee, Arlene, additional, Lee, Kim Y.N., additional, Lees, Emily A., additional, Leung, Stephanie, additional, Li, Yuanyuan, additional, Lias, Amelia M., additional, Linder, Aline, additional, Lipworth, Samuel, additional, Liu, Shuchang, additional, Liu, Xinxue, additional, Lloyd, Stephanie, additional, Loew, Lisa, additional, Lopez Ramon, Raquel, additional, Madhavan, Meera, additional, Mainwaring, David O., additional, Mallett, Garry, additional, Mansatta, Kushal, additional, Marinou, Spyridoula, additional, Marius, Phedra, additional, Marlow, Emma, additional, Marriott, Paula, additional, Marshall, Julia L., additional, Martin, Jane, additional, Masters, Shauna, additional, McEwan, Joanne, additional, McGlashan, Joanna L., additional, McInroy, Lorna, additional, McRobert, Nicky, additional, Megson, Clare, additional, Mentzer, Alexander J., additional, Mirtorabi, Neginsadat, additional, Mitton, Celia, additional, Moore, Maria, additional, Moran, Marni, additional, Morey, Ella, additional, Morgans, Róisín, additional, Morris, Susan J., additional, Morrison, Hazel Morrison, additional, Morshead, Gertraud, additional, Morter, Richard, additional, Moya, Nathifa A., additional, Mukhopadhyay, Ekta, additional, Muller, Jilly, additional, Munro, Claire, additional, Murphy, Sarah, additional, Mweu, Philomena, additional, Noé, Andrés, additional, Nugent, Fay L., additional, O'Brien, Katie, additional, O'Connor, Daniel, additional, Oguti, Blanché, additional, Olchawski, Victoria, additional, Oliveira, Catarina, additional, O'Reilly, Peter John, additional, Osborne, Piper, additional, Owen, Lydia, additional, Owino, Nelly, additional, Papageorgiou, Panagiotis, additional, Parracho, Helena, additional, Parsons, Karen, additional, Patel, Bhumika, additional, Patrick-Smith, Maia, additional, Peng, Yanchun, additional, Penn, Elizabeth J., additional, Peralta-Alvarez, Marco Polo, additional, Perring, James, additional, Petropoulos, Christos, additional, Phillips, Daniel J., additional, Pipini, Dimitra, additional, Pollard, Samuel, additional, Poulton, Ian, additional, Pratt, Danny, additional, Presland, Laura, additional, Proud, Pamela C., additional, Provstgaard-Morys, Samuel, additional, Pueschel, Sophie, additional, Pulido, David, additional, Rabara, Ria, additional, Radia, Kajal, additional, Rajapaska, Durga, additional, Ramos Lopez, Fernando, additional, Ratcliffe, Helen, additional, Rayhan, Sara, additional, Rees, Byron, additional, Reyes Pabon, Emilia, additional, Roberts, Hannah, additional, Robertson, Isla, additional, Roche, Sophie, additional, Rollier, Christine S., additional, Romani, Rossana, additional, Rose, Zoe, additional, Rudiansyah, Indra, additional, Sabheha, Sabeha, additional, Salvador, Stephannie, additional, Sanders, Helen, additional, Sanders, Katherine, additional, Satti, Iman, additional, Sayce, Chloe, additional, Schmid, Annina B., additional, Schofield, Ella, additional, Screaton, Gavin, additional, Sedik, Cynthia, additional, Seddiqi, Samiullah, additional, Segireddy, Rameswara R., additional, Selby, Beatrice, additional, Shaik, Imam, additional, Sharpe, Hannah R., additional, Shaw, Robert, additional, Shea, Adam, additional, Silk, Sarah, additional, Silva-Reyes, Laura, additional, Skelly, Donal T., additional, Smith, David J., additional, Smith, Daniel C., additional, Smith, Nicholas, additional, Spencer, Alexandra J., additional, Spoors, Louise, additional, Stafford, Elizabeth, additional, Stamford, Imogen, additional, Stockdale, Lisa, additional, Stockley, David, additional, Stockwell, Lisa V., additional, Stokes, Matthew, additional, Strickland, Louise H., additional, Stuart, Arabella, additional, Sulaiman, Sulaiman, additional, Summerton, Eloise, additional, Swash, Zoe, additional, Szigeti, Anna, additional, Tahiri-Alaoui, Abdessamad, additional, Tanner, Rachel, additional, Taylor, Iona, additional, Taylor, Keja, additional, Taylor, Ursula, additional, te Water Naude, Rebecca, additional, Themistocleous, Andreas, additional, Thomas, Merin, additional, Thomas, Tonia M., additional, Thompson, Amber, additional, Thompson, Kevin, additional, Thornton-Jones, Viv, additional, Tinh, Lan, additional, Tomic, Adriana, additional, Tonks, Susan, additional, Towner, James, additional, Tran, Nguyen, additional, Tree, Julian A., additional, Truby, Adam, additional, Turner, Cheryl, additional, Turner, Richard, additional, Ulaszewska, Marta, additional, Varughese, Rachel, additional, Verbart, Dennis, additional, Verheul, Marije K., additional, Vichos, Iason, additional, Walker, Laura, additional, Wand, Matthew E., additional, Watkins, Bridget, additional, Welch, Jessica, additional, West, Alison J., additional, White, Caroline, additional, White, Rachel, additional, Williams, Paul, additional, Woodyer, Mark, additional, Worth, Andrew T., additional, Wright, Daniel, additional, Wrin, Terri, additional, Yao, Xin Li, additional, Zbarcea, Diana-Andreea, additional, and Zizi, Dalila, additional
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- 2020
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34. Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial
- Author
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Folegatti, Pedro M, primary, Ewer, Katie J, additional, Aley, Parvinder K, additional, Angus, Brian, additional, Becker, Stephan, additional, Belij-Rammerstorfer, Sandra, additional, Bellamy, Duncan, additional, Bibi, Sagida, additional, Bittaye, Mustapha, additional, Clutterbuck, Elizabeth A, additional, Dold, Christina, additional, Faust, Saul N, additional, Finn, Adam, additional, Flaxman, Amy L, additional, Hallis, Bassam, additional, Heath, Paul, additional, Jenkin, Daniel, additional, Lazarus, Rajeka, additional, Makinson, Rebecca, additional, Minassian, Angela M, additional, Pollock, Katrina M, additional, Ramasamy, Maheshi, additional, Robinson, Hannah, additional, Snape, Matthew, additional, Tarrant, Richard, additional, Voysey, Merryn, additional, Green, Catherine, additional, Douglas, Alexander D, additional, Hill, Adrian V S, additional, Lambe, Teresa, additional, Gilbert, Sarah C, additional, Pollard, Andrew J, additional, Aboagye, Jeremy, additional, Adams, Kelly, additional, Ali, Aabidah, additional, Allen, Elizabeth, additional, Allison, Jennifer L., additional, Anslow, Rachel, additional, Arbe-Barnes, Edward H., additional, Babbage, Gavin, additional, Baillie, Kenneth, additional, Baker, Megan, additional, Baker, Natalie, additional, Baker, Philip, additional, Baleanu, Ioana, additional, Ballaminut, Juliana, additional, Barnes, Eleanor, additional, Barrett, Jordan, additional, Bates, Louise, additional, Batten, Alexander, additional, Beadon, Kirsten, additional, Beckley, Rebecca, additional, Berrie, Eleanor, additional, Berry, Lisa, additional, Beveridge, Amy, additional, Bewley, Kevin R., additional, Bijker, Else Margreet, additional, Bingham, Tracey, additional, Blackwell, Luke, additional, Blundell, Caitlin L., additional, Bolam, Emma, additional, Boland, Elena, additional, Borthwick, Nicola, additional, Bower, Thomas, additional, Boyd, Amy, additional, Brenner, Tanja, additional, Bright, Philip D., additional, Brown-O'Sullivan, Charlie, additional, Brunt, Emily, additional, Burbage, Jamie, additional, Burge, Sharon, additional, Buttigieg, Karen R., additional, Byard, Nicholas, additional, Cabera Puig, Ingrid, additional, Calvert, Anna, additional, Camara, Susana, additional, Cao, Michelangelo, additional, Cappuccini, Federica, additional, Carr, Melanie, additional, Carroll, Miles W., additional, Carter, Victoria, additional, Cathie, Katrina, additional, Challis, Ruth J., additional, Charlton, Sue, additional, Chelysheva, Irina, additional, Cho, Jee-Sun, additional, Cicconi, Paola, additional, Cifuentes, Liliana, additional, Clark, Helen, additional, Clark, Elizabeth, additional, Cole, Tom, additional, Colin-Jones, Rachel, additional, Conlon, Christopher P., additional, Cook, Aislinn, additional, Coombes, Naomi S., additional, Cooper, Rachel, additional, Cosgrove, Catherine A., additional, Coy, Karen, additional, Crocker, Wendy E.M., additional, Cunningham, Christina J., additional, Damratoski, Brad E., additional, Dando, Lynne, additional, Datoo, Mehreen S., additional, Davies, Hannah, additional, De Graaf, Hans, additional, Demissie, Tesfaye, additional, Di Maso, Claudio, additional, Dietrich, Isabelle, additional, Dong, Tao, additional, Donnellan, Francesca R., additional, Douglas, Naomi, additional, Downing, Charlotte, additional, Drake, Jonathan, additional, Drake-Brockman, Rachael, additional, Drury, Ruth Elizabeth, additional, Dunachie, Susanna Jane, additional, Edwards, Nick J., additional, Edwards, Frances D.L., additional, Edwards, Chris J., additional, Elias, Sean C., additional, Elmore, Michael J., additional, Emary, Katherine R.W., additional, English, Marcus Rex, additional, Fagerbrink, Susanne, additional, Felle, Sally, additional, Feng, Shuo, additional, Field, Samantha, additional, Fixmer, Carine, additional, Fletcher, Clare, additional, Ford, Karen J., additional, Fowler, Jamie, additional, Fox, Polly, additional, Francis, Emma, additional, Frater, John, additional, Furze, Julie, additional, Fuskova, Michelle, additional, Galiza, Eva, additional, Gbesemete, Diane, additional, Gilbride, Ciaran, additional, Godwin, Kerry, additional, Gorini, Giacomo, additional, Goulston, Lyndsey, additional, Grabau, Caroline, additional, Gracie, Lara, additional, Gray, Zoe, additional, Guthrie, Lucy Belle, additional, Hackett, Mark, additional, Halwe, Sandro, additional, Hamilton, Elizabeth, additional, Hamlyn, Joseph, additional, Hanumunthadu, Brama, additional, Harding, Irasha, additional, Harris, Stephanie A., additional, Harris, Andrew, additional, Harrison, Daisy, additional, Harrison, Clare, additional, Hart, Thomas C., additional, Haskell, Louise, additional, Hawkins, Sophia, additional, Head, Ian, additional, Henry, John Aaron, additional, Hill, Jennifer, additional, Hodgson, Susanne H.C., additional, Hou, Mimi M., additional, Howe, Elizabeth, additional, Howell, Nicola, additional, Hutlin, Cecilia, additional, Ikram, Sabina, additional, Isitt, Catherine, additional, Iveson, Poppy, additional, Jackson, Susan, additional, Jackson, Frederic, additional, James, Sir William, additional, Jenkins, Megan, additional, Jones, Elizabeth, additional, Jones, Kathryn, additional, Jones, Christine E., additional, Jones, Bryony, additional, Kailath, Reshma, additional, Karampatsas, Konstantinos, additional, Keen, Jade, additional, Kelly, Sarah, additional, Kelly, Dearbhla, additional, Kerr, David, additional, Kerridge, Simon, additional, Khan, Liaquat, additional, Khan, Uzma, additional, Killen, Annabel, additional, Kinch, Jasmin, additional, King, Thomas B., additional, King, Lloyd, additional, King, Jade, additional, Kingham-Page, Lucy, additional, Klenerman, Paul, additional, Knapper, Francesca, additional, Knight, Julian C., additional, Knott, Daniel, additional, Koleva, Stanislava, additional, Kupke, Alexandra, additional, Larkworthy, Colin W., additional, Larwood, Jessica P.J., additional, Laskey, Anna, additional, Lawrie, Alison M., additional, Lee, Arlene, additional, Ngan Lee, Kim Yee, additional, Lees, Emily A, additional, Legge, Helen, additional, Lelliott, Alice, additional, Lemm, Nana-Marie, additional, Lias, Amelia M., additional, Linder, Aline, additional, Lipworth, Samuel, additional, Liu, Xinxue, additional, Liu, Shuchang, additional, Lopez Ramon, Raquel, additional, Lwin, May, additional, Mabesa, Francesca, additional, Madhavan, Meera, additional, Mallett, Garry, additional, Mansatta, Kushal, additional, Marcal, Ines, additional, Marinou, Spyridoula, additional, Marlow, Emma, additional, Marshall, Julia L., additional, Martin, Jane, additional, McEwan, Joanne, additional, McInroy, Lorna, additional, Meddaugh, Gretchen, additional, Mentzer, Alexander J., additional, Mirtorabi, Neginsadat, additional, Moore, Maria, additional, Moran, Edward, additional, Morey, Ella, additional, Morgan, Victoria, additional, Morris, Susan Jane, additional, Morrison, Hazel, additional, Morshead, Gertraud, additional, Morter, Richard, additional, Mujadidi, Yama F., additional, Muller, Jilly, additional, Munera-Huertas, Tatiana, additional, Munro, Claire, additional, Munro, Alasdair, additional, Murphy, Sarah, additional, Munster, Vincent J., additional, Mweu, Philomena, additional, Noé, Andrés, additional, Nugent, Fay L., additional, Nuthall, Elizabeth, additional, O'Brien, Katie, additional, O'Connor, Daniel, additional, Oguti, Blanché, additional, Oliver, Jennifer L., additional, Oliveira, Catarina, additional, O'Reilly, Peter John, additional, Osborn, Mairead, additional, Osborne, Piper, additional, Owen, Cathy, additional, Owens, Daniel, additional, Owino, Nelly, additional, Pacurar, Mihaela, additional, Parker, Kaye, additional, Parracho, Helena, additional, Patrick-Smith, Maia, additional, Payne, Victoria, additional, Pearce, Jennifer, additional, Peng, Yanchun, additional, Peralta Alvarez, Marco Polo, additional, Perring, James, additional, Pfafferott, Katja, additional, Pipini, Dimitra, additional, Plested, Emma, additional, Pluess-Hall, Helen, additional, Pollock, Katrina, additional, Poulton, Ian, additional, Presland, Laura, additional, Provstgaard-Morys, Samuel, additional, Pulido, David, additional, Radia, Kajal, additional, Ramos Lopez, Fernando, additional, Rand, Jade, additional, Ratcliffe, Helen, additional, Rawlinson, Thomas, additional, Rhead, Sarah, additional, Riddell, Amy, additional, Ritchie, Adam John, additional, Roberts, Hannah, additional, Robson, Joanna, additional, Roche, Sophie, additional, Rohde, Cornelius, additional, Rollier, Christine S., additional, Romani, Rossana, additional, Rudiansyah, Indra, additional, Saich, Stephen, additional, Sajjad, Sara, additional, Salvador, Stephannie, additional, Sanchez Riera, Lidia, additional, Sanders, Helen, additional, Sanders, Katherine, additional, Sapaun, Shari, additional, Sayce, Chloe, additional, Schofield, Ella, additional, Screaton, Gavin, additional, Selby, Beatrice, additional, Semple, Calum, additional, Sharpe, Hannah R., additional, Shaik, Imam, additional, Shea, Adam, additional, Shelton, Holly, additional, Silk, Sarah, additional, Silva-Reyes, Laura, additional, Skelly, Donal T., additional, Smee, Heather, additional, Smith, Catherine C., additional, Smith, David J., additional, Song, Rinn, additional, Spencer, Alexandra J., additional, Stafford, Elizabeth, additional, Steele, Amy, additional, Stefanova, Elena, additional, Stockdale, Lisa, additional, Szigeti, Anna, additional, Tahiri-Alaoui, Abdessamad, additional, Tait, Moira, additional, Talbot, Helen, additional, Tanner, Rachel, additional, Taylor, Iona Jennifer, additional, Taylor, Victoria, additional, Te Water Naude, Rebecca, additional, Thakur, Nazia, additional, Themistocleous, Yrene, additional, Themistocleous, Andreas, additional, Thomas, Merin, additional, Thomas, Tonia M., additional, Thompson, Amber, additional, Thomson-Hill, Samantha, additional, Tomlins, Jennifer, additional, Tonks, Susan, additional, Towner, James, additional, Tran, Nguyen, additional, Tree, Julia A., additional, Truby, Adam, additional, Turkentine, Kate, additional, Turner, Cheryl, additional, Turner, Nicola, additional, Turner, Sally, additional, Tuthill, Toby, additional, Ulaszewska, Marta, additional, Varughese, Rachel, additional, Van Doremalen, Neeltje, additional, Veighey, Kristin, additional, Verheul, Marije K., additional, Vichos, Iason, additional, Vitale, Elia, additional, Walker, Laura, additional, Watson, Marion E.E., additional, Welham, Benjamin, additional, Wheat, Julie, additional, White, Caroline, additional, White, Rachel, additional, Worth, Andrew T., additional, Wright, Danny, additional, Wright, Suzie, additional, Yao, Xin Li, additional, and Yau, Yasmine, additional
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- 2020
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35. Safety and Immunogenicity of a Novel Recombinant Simian Adenovirus ChAdOx2 as a Vectored Vaccine
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Folegatti, Pedro M., primary, Bellamy, Duncan, additional, Roberts, Rachel, additional, Powlson, Jonathan, additional, Edwards, Nick J., additional, Mair, Catherine F., additional, Bowyer, Georgina, additional, Poulton, Ian, additional, Mitton, Celia H., additional, Green, Nicky, additional, Berrie, Eleanor, additional, Lawrie, Alison M., additional, Hill, Adrian V.S., additional, Ewer, Katie J., additional, Hermon-Taylor, John, additional, and Gilbert, Sarah C., additional
- Published
- 2019
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36. Safety and Immunogenicity of the Heterosubtypic Influenza A Vaccine MVA-NP+M1 Manufactured on the AGE1.CR.pIX Avian Cell Line
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Folegatti, Pedro M., primary, Bellamy, Duncan, additional, Flaxman, Amy, additional, Mair, Catherine, additional, Ellis, Chris, additional, Ramon, Raquel L., additional, Ramos Lopez, Fernando, additional, Mitton, Celia, additional, Baker, Megan, additional, Poulton, Ian, additional, Lawrie, Alison, additional, Roberts, Rachel, additional, Minassian, Angela, additional, Ewer, Katie J., additional, Evans, Thomas G., additional, Hill, Adrian V. S., additional, and Gilbert, Sarah C., additional
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- 2019
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37. Vaccines against Ebola virus
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Venkatraman, Navin, primary, Silman, Daniel, additional, Folegatti, Pedro M., additional, and Hill, Adrian V.S., additional
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- 2018
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38. T cell and antibody responses induced by a single dose of ChAdOx1 nCoV-19 (AZD1222) vaccine in a phase 1/2 clinical trial
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Ewer, Katie J., Barrett, Jordan R., Belij-Rammerstorfer, Sandra, Sharpe, Hannah, Makinson, Rebecca, Morter, Richard, Flaxman, Amy, Wright, Daniel, Bellamy, Duncan, Bittaye, Mustapha, Dold, Christina, Provine, Nicholas M., Aboagye, Jeremy, Fowler, Jamie, Silk, Sarah E., Alderson, Jennifer, Aley, Parvinder K., Angus, Brian, Berrie, Eleanor, Bibi, Sagida, Cicconi, Paola, Clutterbuck, Elizabeth A., Chelysheva, Irina, Folegatti, Pedro M., Fuskova, Michelle, Green, Catherine M., Jenkin, Daniel, Kerridge, Simon, Lawrie, Alison, Minassian, Angela M., Moore, Maria, Mujadidi, Yama, Plested, Emma, Poulton, Ian, Ramasamy, Maheshi N., Robinson, Hannah, Song, Rinn, Snape, Matthew D., Tarrant, Richard, Voysey, Merryn, Watson, Marion E. E., Douglas, Alexander D., Hill, Adrian V. S., Gilbert, Sarah C., Pollard, Andrew J., and Lambe, Teresa
- Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus Disease 2019 (COVID-19), has caused a global pandemic, and safe, effective vaccines are urgently needed1. Strong, Th1-skewed T cell responses can drive protective humoral and cell-mediated immune responses2and might reduce the potential for disease enhancement3. Cytotoxic T cells clear virus-infected host cells and contribute to control of infection4. Studies of patients infected with SARS-CoV-2 have suggested a protective role for both humoral and cell-mediated immune responses in recovery from COVID-19 (refs. 5,6). ChAdOx1 nCoV-19 (AZD1222) is a candidate SARS-CoV-2 vaccine comprising a replication-deficient simian adenovirus expressing full-length SARS-CoV-2 spike protein. We recently reported preliminary safety and immunogenicity data from a phase 1/2 trial of the ChAdOx1 nCoV-19 vaccine (NCT04400838)7given as either a one- or two-dose regimen. The vaccine was tolerated, with induction of neutralizing antibodies and antigen-specific T cells against the SARS-CoV-2 spike protein. Here we describe, in detail, exploratory analyses of the immune responses in adults, aged 18–55 years, up to 8 weeks after vaccination with a single dose of ChAdOx1 nCoV-19 in this trial, demonstrating an induction of a Th1-biased response characterized by interferon-γ and tumor necrosis factor-α cytokine secretion by CD4+T cells and antibody production predominantly of IgG1 and IgG3 subclasses. CD8+T cells, of monofunctional, polyfunctional and cytotoxic phenotypes, were also induced. Taken together, these results suggest a favorable immune profile induced by ChAdOx1 nCoV-19 vaccine, supporting the progression of this vaccine candidate to ongoing phase 2/3 trials to assess vaccine efficacy.
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- 2021
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39. A systematic review on malaria sero-epidemiology studies in the Brazilian Amazon: insights into immunological markers for exposure and protection
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Folegatti, Pedro M., primary, Siqueira, André M., additional, Monteiro, Wuelton M., additional, Lacerda, Marcus Vinícius G., additional, Drakeley, Chris J., additional, and Braga, Érika M., additional
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- 2017
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40. Efficacy and Safety of a Modified Vaccinia Ankara-NP+M1 Vaccine Combined with QIV in People Aged 65 and Older: A Randomised Controlled Clinical Trial (INVICTUS).
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Butler, Chris, Ellis, Chris, Folegatti, Pedro M., Swayze, Hannah, Allen, Julie, Bussey, Louise, Bellamy, Duncan, Lawrie, Alison, Eagling-Vose, Elizabeth, Yu, Ly-Mee, Shanyinde, Milensu, Mair, Catherine, Flaxman, Amy, Ewer, Katie, Gilbert, Sarah, and Evans, Thomas G.
- Subjects
CLINICAL trials ,RANDOMIZED controlled trials ,OLDER people ,VACCINIA ,INFLUENZA vaccines - Abstract
Background: Pre-existing T cell responses to influenza have been correlated with improved clinical outcomes in natural history and human challenge studies. We aimed to determine the efficacy, safety and immunogenicity of a T-cell directed vaccine in older people. Methods: This was a multicentre, participant- and safety assessor-blinded, randomised, placebo-controlled trial of the co-administration of Modified Vaccinia Ankara encoding nucleoprotein and matrix protein 1 (MVA-NP+M1) and annual influenza vaccine in participants ≥ 65. The primary outcome was the number of days with moderate or severe influenza-like symptoms (ILS) during the influenza season. Results: 846 of a planned 2030 participants were recruited in the UK prior to, and throughout, the 2017/18 flu season. There was no evidence of a difference in the reported rates of days of moderate or severe ILS during influenza-like illness episodes (unadjusted OR = 0.95, 95% CI: 0.54–1.69; adjusted OR = 0.91, 95% CI: 0.51–1.65). The trial was stopped after one season due to a change in the recommended annual flu vaccine, for which safety of the new combination had not been established. More participants in the MVA-NP+M1 group had transient moderate or severe pain, redness, and systemic responses in the first seven days. Conclusion: The MVA-NP+M1 vaccine is well tolerated in those aged 65 years and over. Larger trials would be needed to determine potential efficacy. [ABSTRACT FROM AUTHOR]
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- 2021
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41. Author Correction: T cell and antibody responses induced by a single dose of ChAdOx1 nCoV-19 (AZD1222) vaccine in a phase 1/2 clinical trial
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Ewer, Katie J., Barrett, Jordan R., Belij-Rammerstorfer, Sandra, Sharpe, Hannah, Makinson, Rebecca, Morter, Richard, Flaxman, Amy, Wright, Daniel, Bellamy, Duncan, Bittaye, Mustapha, Dold, Christina, Provine, Nicholas M., Aboagye, Jeremy, Fowler, Jamie, Silk, Sarah E., Alderson, Jennifer, Aley, Parvinder K., Angus, Brian, Berrie, Eleanor, Bibi, Sagida, Cicconi, Paola, Clutterbuck, Elizabeth A., Chelysheva, Irina, Folegatti, Pedro M., Fuskova, Michelle, Green, Catherine M., Jenkin, Daniel, Kerridge, Simon, Lawrie, Alison, Minassian, Angela M., Moore, Maria, Mujadidi, Yama, Plested, Emma, Poulton, Ian, Ramasamy, Maheshi N., Robinson, Hannah, Song, Rinn, Snape, Matthew D., Tarrant, Richard, Voysey, Merryn, Watson, Marion E. E., Douglas, Alexander D., Hill, Adrian V. S., Gilbert, Sarah C., Pollard, Andrew J., and Lambe, Teresa
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- 2021
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42. Efficacy of ChAdOx1 nCoV-19 (AZD1222) Vaccine Against SARS-CoV-2 VOC 202012/01 (B.1.1.7)
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Emary, Katherine RW, Golubchik, Tanya, Aley, Parvinder K, Ariani, Cristina V, Angus, Brian John, Bibi, Sagida, Blane, Beth, Bonsall, David, Cicconi, Paola, Charlton, Sue, Clutterbuck, Elizabeth, Collins, Andrea M, Cox, Tony, Darton, Thomas, Dold, Christina, Douglas, Alexander D, Duncan, Christopher JA, Ewer, Katie, Flaxman, Amy, Faust, Saul N, Ferreira, Daniela M, Feng, Shuo, Finn, Adam, Folegatti, Pedro M, Fuskova, Michelle, Galiza, Eva, Goodman, Anna L, Green, Catherine M, Green, Christopher A, Greenland, Melanie, Hallis, Bassam, Heath, Paul T, Hay, Jodie, Hill, Helen C, Jenkin, Daniel, Kerridge, Simon, Lazarus, Rajeka, Libri, Vincenzo, Lillie, Patrick J, Ludden, Catherine, Marchevsky, Natalie, Minassian, Angela M, McGregor, Alastair C, Farooq Mujadidi, Yama, Phillips, Daniel J, Plested, Emma, Pollock, Katrina M, Robinson, Hannah, Smith, Andrew, Song, Rinn, Snape, Matthew D, Sutherland, Rebecca K, Thomson, Emma C, Toshner, Mark, Turner, David PJ, Vekemans, Johan, Villafana, Tonya L, Williams, Christopher J, Hill, Adrian VS, Lambe, Teresa, Gilbert, Sarah C, Voysey, Merryn, Ramasamy, Maheshi N, Pollard, Andrew, Consortium, COVID-19 Genomics UK COG-UK, Group, Oxford COVID Vaccine Trial, Toshner, Mark [0000-0002-3969-6143], and Apollo - University of Cambridge Repository
43. Single Dose Administration, And The Influence Of The Timing Of The Booster Dose On Immunogenicity and Efficacy Of ChAdOx1 nCoV-19 (AZD1222) Vaccine
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Voysey, Merryn, Costa Clemens, Sue Ann, Madhi, Shabir A, Weckx, Lily Yin, Folegatti, Pedro M, Aley, Parvinder K, Angus, Brian John, Baillie, Vicky, Barnabas, Shaun L, Bhorat, Qasim E, Bibi, Sagida, Briner, Carmen, Cicconi, Paola, Clutterbuck, Elizabeth, Collins, Andrea M, Cutland, Clare, Darton, Thomas, Dheda, Keertan, Douglas, Alexander D, Duncan, Christopher JA, Emary, Katherine RW, Ewer, Katie, Flaxman, Amy, Fairlie, Lee, Faust, Saul N, Feng, Shuo, Ferreira, Daniela M, Finn, Adam, Galiza, Eva, Goodman, Anna L, Green, Catherine M, Green, Christopher A, Greenland, Melanie, Hill, Catherine, Hill, Helen C, Hirsch, Ian, Izu, Alane, Jenkin, Daniel, Kerridge, Simon, Koen, Anthonet, Kwatra, Gaurav, Lazarus, Rajeka, Libri, Vincenzo, Lillie, Patrick J, Marchevsky, Natalie, Marshall, Richard P, Mendes, Ana Verena Almeida, Milan, Eveline P, Minassian, Angela M, McGregor, Alastair C, Farooq Mujadidi, Yama, Nana, Anusha, Payadachee, Sherman D, Phillips, Daniel J, Pittella, Ana, Plested, Emma, Pollock, Katrina M, Ramasamy, Maheshi N, Robinson, Hannah, Schwarzbold, Alexandre V, Smith, Andrew, Song, Rinn, Snape, Matthew D, Sprinz, Eduardo, Sutherland, Rebecca K, Thomson, Emma C, Török, Mili Estée, Toshner, Mark, Turner, David PJ, Vekemans, Johan, Villafana, Tonya L, White, Thomas, Williams, Christopher J, Hill, Adrian VS, Lambe, Teresa, Gilbert, Sarah C, Pollard, Andrew, Group, Oxford COVID Vaccine Trial, Toshner, Mark [0000-0002-3969-6143], and Apollo - University of Cambridge Repository
44. Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial.
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Ramasamy MN, Minassian AM, Ewer KJ, Flaxman AL, Folegatti PM, Owens DR, Voysey M, Aley PK, Angus B, Babbage G, Belij-Rammerstorfer S, Berry L, Bibi S, Bittaye M, Cathie K, Chappell H, Charlton S, Cicconi P, Clutterbuck EA, Colin-Jones R, Dold C, Emary KRW, Fedosyuk S, Fuskova M, Gbesemete D, Green C, Hallis B, Hou MM, Jenkin D, Joe CCD, Kelly EJ, Kerridge S, Lawrie AM, Lelliott A, Lwin MN, Makinson R, Marchevsky NG, Mujadidi Y, Munro APS, Pacurar M, Plested E, Rand J, Rawlinson T, Rhead S, Robinson H, Ritchie AJ, Ross-Russell AL, Saich S, Singh N, Smith CC, Snape MD, Song R, Tarrant R, Themistocleous Y, Thomas KM, Villafana TL, Warren SC, Watson MEE, Douglas AD, Hill AVS, Lambe T, Gilbert SC, Faust SN, and Pollard AJ
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- Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, COVID-19 prevention & control, COVID-19 Vaccines adverse effects, COVID-19 Vaccines pharmacology, ChAdOx1 nCoV-19, Female, Humans, Immunization, Secondary adverse effects, Immunoglobulin G blood, Immunoglobulin G drug effects, Male, Middle Aged, SARS-CoV-2 drug effects, Single-Blind Method, Young Adult, COVID-19 Vaccines administration & dosage, Immunogenicity, Vaccine
- Abstract
Background: Older adults (aged ≥70 years) are at increased risk of severe disease and death if they develop COVID-19 and are therefore a priority for immunisation should an efficacious vaccine be developed. Immunogenicity of vaccines is often worse in older adults as a result of immunosenescence. We have reported the immunogenicity of a novel chimpanzee adenovirus-vectored vaccine, ChAdOx1 nCoV-19 (AZD1222), in young adults, and now describe the safety and immunogenicity of this vaccine in a wider range of participants, including adults aged 70 years and older., Methods: In this report of the phase 2 component of a single-blind, randomised, controlled, phase 2/3 trial (COV002), healthy adults aged 18 years and older were enrolled at two UK clinical research facilities, in an age-escalation manner, into 18-55 years, 56-69 years, and 70 years and older immunogenicity subgroups. Participants were eligible if they did not have severe or uncontrolled medical comorbidities or a high frailty score (if aged ≥65 years). First, participants were recruited to a low-dose cohort, and within each age group, participants were randomly assigned to receive either intramuscular ChAdOx1 nCoV-19 (2·2 × 10
10 virus particles) or a control vaccine, MenACWY, using block randomisation and stratified by age and dose group and study site, using the following ratios: in the 18-55 years group, 1:1 to either two doses of ChAdOx1 nCoV-19 or two doses of MenACWY; in the 56-69 years group, 3:1:3:1 to one dose of ChAdOx1 nCoV-19, one dose of MenACWY, two doses of ChAdOx1 nCoV-19, or two doses of MenACWY; and in the 70 years and older, 5:1:5:1 to one dose of ChAdOx1 nCoV-19, one dose of MenACWY, two doses of ChAdOx1 nCoV-19, or two doses of MenACWY. Prime-booster regimens were given 28 days apart. Participants were then recruited to the standard-dose cohort (3·5-6·5 × 1010 virus particles of ChAdOx1 nCoV-19) and the same randomisation procedures were followed, except the 18-55 years group was assigned in a 5:1 ratio to two doses of ChAdOx1 nCoV-19 or two doses of MenACWY. Participants and investigators, but not staff administering the vaccine, were masked to vaccine allocation. The specific objectives of this report were to assess the safety and humoral and cellular immunogenicity of a single-dose and two-dose schedule in adults older than 55 years. Humoral responses at baseline and after each vaccination until 1 year after the booster were assessed using an in-house standardised ELISA, a multiplex immunoassay, and a live severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) microneutralisation assay (MNA80 ). Cellular responses were assessed using an ex-vivo IFN-γ enzyme-linked immunospot assay. The coprimary outcomes of the trial were efficacy, as measured by the number of cases of symptomatic, virologically confirmed COVID-19, and safety, as measured by the occurrence of serious adverse events. Analyses were by group allocation in participants who received the vaccine. Here, we report the preliminary findings on safety, reactogenicity, and cellular and humoral immune responses. This study is ongoing and is registered with ClinicalTrials.gov, NCT04400838, and ISRCTN, 15281137., Findings: Between May 30 and Aug 8, 2020, 560 participants were enrolled: 160 aged 18-55 years (100 assigned to ChAdOx1 nCoV-19, 60 assigned to MenACWY), 160 aged 56-69 years (120 assigned to ChAdOx1 nCoV-19: 40 assigned to MenACWY), and 240 aged 70 years and older (200 assigned to ChAdOx1 nCoV-19: 40 assigned to MenACWY). Seven participants did not receive the boost dose of their assigned two-dose regimen, one participant received the incorrect vaccine, and three were excluded from immunogenicity analyses due to incorrectly labelled samples. 280 (50%) of 552 analysable participants were female. Local and systemic reactions were more common in participants given ChAdOx1 nCoV-19 than in those given the control vaccine, and similar in nature to those previously reported (injection-site pain, feeling feverish, muscle ache, headache), but were less common in older adults (aged ≥56 years) than younger adults. In those receiving two standard doses of ChAdOx1 nCoV-19, after the prime vaccination local reactions were reported in 43 (88%) of 49 participants in the 18-55 years group, 22 (73%) of 30 in the 56-69 years group, and 30 (61%) of 49 in the 70 years and older group, and systemic reactions in 42 (86%) participants in the 18-55 years group, 23 (77%) in the 56-69 years group, and 32 (65%) in the 70 years and older group. As of Oct 26, 2020, 13 serious adverse events occurred during the study period, none of which were considered to be related to either study vaccine. In participants who received two doses of vaccine, median anti-spike SARS-CoV-2 IgG responses 28 days after the boost dose were similar across the three age cohorts (standard-dose groups: 18-55 years, 20 713 arbitrary units [AU]/mL [IQR 13 898-33 550], n=39; 56-69 years, 16 170 AU/mL [10 233-40 353], n=26; and ≥70 years 17 561 AU/mL [9705-37 796], n=47; p=0·68). Neutralising antibody titres after a boost dose were similar across all age groups (median MNA80 at day 42 in the standard-dose groups: 18-55 years, 193 [IQR 113-238], n=39; 56-69 years, 144 [119-347], n=20; and ≥70 years, 161 [73-323], n=47; p=0·40). By 14 days after the boost dose, 208 (>99%) of 209 boosted participants had neutralising antibody responses. T-cell responses peaked at day 14 after a single standard dose of ChAdOx1 nCoV-19 (18-55 years: median 1187 spot-forming cells [SFCs] per million peripheral blood mononuclear cells [IQR 841-2428], n=24; 56-69 years: 797 SFCs [383-1817], n=29; and ≥70 years: 977 SFCs [458-1914], n=48)., Interpretation: ChAdOx1 nCoV-19 appears to be better tolerated in older adults than in younger adults and has similar immunogenicity across all age groups after a boost dose. Further assessment of the efficacy of this vaccine is warranted in all age groups and individuals with comorbidities., Funding: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midlands NIHR Clinical Research Network, and AstraZeneca., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)- Published
- 2021
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45. Efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 lineages circulating in Brazil.
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Clemens SAC, Folegatti PM, Emary KRW, Weckx LY, Ratcliff J, Bibi S, De Almeida Mendes AV, Milan EP, Pittella A, Schwarzbold AV, Sprinz E, Aley PK, Bonsall D, Fraser C, Fuskova M, Gilbert SC, Jenkin D, Kelly S, Kerridge S, Lambe T, Marchevsky NG, Mujadidi YF, Plested E, Ramasamy MN, Simmonds P, Golubchik T, Voysey M, and Pollard AJ
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- Adolescent, Adult, Aged, Brazil, ChAdOx1 nCoV-19, Cohort Studies, Dose-Response Relationship, Immunologic, Female, Hospitalization, Humans, Male, Middle Aged, Treatment Outcome, Vaccination, Viral Load immunology, Young Adult, COVID-19 immunology, COVID-19 virology, COVID-19 Vaccines immunology, Phylogeny, SARS-CoV-2 immunology
- Abstract
Several COVID-19 vaccines have shown good efficacy in clinical trials, but there remains uncertainty about the efficacy of vaccines against different variants. Here, we investigate the efficacy of ChAdOx1 nCoV-19 (AZD1222) against symptomatic COVID-19 in a post-hoc exploratory analysis of a Phase 3 randomised trial in Brazil (trial registration ISRCTN89951424). Nose and throat swabs were tested by PCR in symptomatic participants. Sequencing and genotyping of swabs were performed to determine the lineages of SARS-CoV-2 circulating during the study. Protection against any symptomatic COVID-19 caused by the Zeta (P.2) variant was assessed in 153 cases with vaccine efficacy (VE) of 69% (95% CI 55, 78). 49 cases of B.1.1.28 occurred and VE was 73% (46, 86). The Gamma (P.1) variant arose later in the trial and fewer cases (N = 18) were available for analysis. VE was 64% (-2, 87). ChAdOx1 nCoV-19 provided 95% protection (95% CI 61%, 99%) against hospitalisation due to COVID-19. In summary, we report that ChAdOx1 nCoV-19 protects against emerging variants in Brazil despite the presence of the spike protein mutation E484K., (© 2021. The Author(s).)
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46. Reactogenicity and immunogenicity after a late second dose or a third dose of ChAdOx1 nCoV-19 in the UK: a substudy of two randomised controlled trials (COV001 and COV002).
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Flaxman A, Marchevsky NG, Jenkin D, Aboagye J, Aley PK, Angus B, Belij-Rammerstorfer S, Bibi S, Bittaye M, Cappuccini F, Cicconi P, Clutterbuck EA, Davies S, Dejnirattisai W, Dold C, Ewer KJ, Folegatti PM, Fowler J, Hill AVS, Kerridge S, Minassian AM, Mongkolsapaya J, Mujadidi YF, Plested E, Ramasamy MN, Robinson H, Sanders H, Sheehan E, Smith H, Snape MD, Song R, Woods D, Screaton G, Gilbert SC, Voysey M, Pollard AJ, and Lambe T
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- Adult, ChAdOx1 nCoV-19, Female, Humans, Leukocytes, Mononuclear immunology, Male, Middle Aged, Time Factors, United Kingdom, COVID-19 Vaccines administration & dosage, Immunogenicity, Vaccine immunology, Randomized Controlled Trials as Topic, Vaccination
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Background: COVID-19 vaccine supply shortages are causing concerns about compromised immunity in some countries as the interval between the first and second dose becomes longer. Conversely, countries with no supply constraints are considering administering a third dose. We assessed the persistence of immunogenicity after a single dose of ChAdOx1 nCoV-19 (AZD1222), immunity after an extended interval (44-45 weeks) between the first and second dose, and response to a third dose as a booster given 28-38 weeks after the second dose., Methods: In this substudy, volunteers aged 18-55 years who were enrolled in the phase 1/2 (COV001) controlled trial in the UK and had received either a single dose or two doses of 5 × 10
10 viral particles were invited back for vaccination. Here we report the reactogenicity and immunogenicity of a delayed second dose (44-45 weeks after first dose) or a third dose of the vaccine (28-38 weeks after second dose). Data from volunteers aged 18-55 years who were enrolled in either the phase 1/2 (COV001) or phase 2/3 (COV002), single-blinded, randomised controlled trials of ChAdOx1 nCoV-19 and who had previously received a single dose or two doses of 5 × 1010 viral particles are used for comparison purposes. COV001 is registered with ClinicalTrials.gov, NCT04324606, and ISRCTN, 15281137, and COV002 is registered with ClinicalTrials.gov, NCT04400838, and ISRCTN, 15281137, and both are continuing but not recruiting., Findings: Between March 11 and 21, 2021, 90 participants were enrolled in the third-dose boost substudy, of whom 80 (89%) were assessable for reactogenicity, 75 (83%) were assessable for evaluation of antibodies, and 15 (17%) were assessable for T-cells responses. The two-dose cohort comprised 321 participants who had reactogenicity data (with prime-boost interval of 8-12 weeks: 267 [83%] of 321; 15-25 weeks: 24 [7%]; or 44-45 weeks: 30 [9%]) and 261 who had immunogenicity data (interval of 8-12 weeks: 115 [44%] of 261; 15-25 weeks: 116 [44%]; and 44-45 weeks: 30 [11%]). 480 participants from the single-dose cohort were assessable for immunogenicity up to 44-45 weeks after vaccination. Antibody titres after a single dose measured approximately 320 days after vaccination remained higher than the titres measured at baseline (geometric mean titre of 66·00 ELISA units [EUs; 95% CI 47·83-91·08] vs 1·75 EUs [1·60-1·93]). 32 participants received a late second dose of vaccine 44-45 weeks after the first dose, of whom 30 were included in immunogenicity and reactogenicity analyses. Antibody titres were higher 28 days after vaccination in those with a longer interval between first and second dose than for those with a short interval (median total IgG titre: 923 EUs [IQR 525-1764] with an 8-12 week interval; 1860 EUs [917-4934] with a 15-25 week interval; and 3738 EUs [1824-6625] with a 44-45 week interval). Among participants who received a third dose of vaccine, antibody titres (measured in 73 [81%] participants for whom samples were available) were significantly higher 28 days after a third dose (median total IgG titre: 3746 EUs [IQR 2047-6420]) than 28 days after a second dose (median 1792 EUs [IQR 899-4634]; Wilcoxon signed rank test p=0·0043). T-cell responses were also boosted after a third dose (median response increased from 200 spot forming units [SFUs] per million peripheral blood mononuclear cells [PBMCs; IQR 127-389] immediately before the third dose to 399 SFUs per milion PBMCs [314-662] by day 28 after the third dose; Wilcoxon signed rank test p=0·012). Reactogenicity after a late second dose or a third dose was lower than reactogenicity after a first dose., Interpretation: An extended interval before the second dose of ChAdOx1 nCoV-19 leads to increased antibody titres. A third dose of ChAdOx1 nCoV-19 induces antibodies to a level that correlates with high efficacy after second dose and boosts T-cell responses., Funding: UK Research and Innovation, Engineering and Physical Sciences Research Council, National Institute for Health Research, Coalition for Epidemic Preparedness Innovations, National Institute for Health Research Oxford Biomedical Research Centre, Chinese Academy of Medical Sciences Innovation Fund for Medical Science, Thames Valley and South Midlands NIHR Clinical Research Network, AstraZeneca, and Wellcome., Competing Interests: Declaration of interests SCG and AVSH are cofounders of and shareholders in Vaccitech (collaborators in the early development of ChAdOx1 nCoV-19) and named as inventors on a patent covering use of ChAdOx1-vectored vaccines (PCT/GB2012/000467) and a patent application covering this SARS-CoV-2 vaccine (SCG only). TL is named as an inventor on a patent covering use of ChAdOx1-vectored vaccines (PCT/GB2012/000467) and was a consultant to Vaccitech. PMF is a consultant to Vaccitech. AJP is chair of the UK Department of Health and Social Care's Joint Committee on Vaccination and Immunisation, but does not participate in policy advice on coronavirus vaccines, and is a member of the WHO Strategic Advisory Group of Experts (SAGE). AJP is an NIHR Senior Investigator. All other authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)- Published
- 2021
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47. Efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 variant of concern 202012/01 (B.1.1.7): an exploratory analysis of a randomised controlled trial.
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Emary KRW, Golubchik T, Aley PK, Ariani CV, Angus B, Bibi S, Blane B, Bonsall D, Cicconi P, Charlton S, Clutterbuck EA, Collins AM, Cox T, Darton TC, Dold C, Douglas AD, Duncan CJA, Ewer KJ, Flaxman AL, Faust SN, Ferreira DM, Feng S, Finn A, Folegatti PM, Fuskova M, Galiza E, Goodman AL, Green CM, Green CA, Greenland M, Hallis B, Heath PT, Hay J, Hill HC, Jenkin D, Kerridge S, Lazarus R, Libri V, Lillie PJ, Ludden C, Marchevsky NG, Minassian AM, McGregor AC, Mujadidi YF, Phillips DJ, Plested E, Pollock KM, Robinson H, Smith A, Song R, Snape MD, Sutherland RK, Thomson EC, Toshner M, Turner DPJ, Vekemans J, Villafana TL, Williams CJ, Hill AVS, Lambe T, Gilbert SC, Voysey M, Ramasamy MN, and Pollard AJ
- Subjects
- Adolescent, Adult, COVID-19 epidemiology, COVID-19 Nucleic Acid Testing, COVID-19 Vaccines adverse effects, ChAdOx1 nCoV-19, Female, Humans, Male, Middle Aged, Nucleic Acid Amplification Techniques, Pandemics prevention & control, Single-Blind Method, United Kingdom epidemiology, Viral Load, Young Adult, Antibodies, Neutralizing blood, COVID-19 prevention & control, COVID-19 virology, COVID-19 Vaccines immunology, SARS-CoV-2 immunology
- Abstract
Background: A new variant of SARS-CoV-2, B.1.1.7, emerged as the dominant cause of COVID-19 disease in the UK from November, 2020. We report a post-hoc analysis of the efficacy of the adenoviral vector vaccine, ChAdOx1 nCoV-19 (AZD1222), against this variant., Methods: Volunteers (aged ≥18 years) who were enrolled in phase 2/3 vaccine efficacy studies in the UK, and who were randomly assigned (1:1) to receive ChAdOx1 nCoV-19 or a meningococcal conjugate control (MenACWY) vaccine, provided upper airway swabs on a weekly basis and also if they developed symptoms of COVID-19 disease (a cough, a fever of 37·8°C or higher, shortness of breath, anosmia, or ageusia). Swabs were tested by nucleic acid amplification test (NAAT) for SARS-CoV-2 and positive samples were sequenced through the COVID-19 Genomics UK consortium. Neutralising antibody responses were measured using a live-virus microneutralisation assay against the B.1.1.7 lineage and a canonical non-B.1.1.7 lineage (Victoria). The efficacy analysis included symptomatic COVID-19 in seronegative participants with a NAAT positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to vaccine received. Vaccine efficacy was calculated as 1 - relative risk (ChAdOx1 nCoV-19 vs MenACWY groups) derived from a robust Poisson regression model. This study is continuing and is registered with ClinicalTrials.gov, NCT04400838, and ISRCTN, 15281137., Findings: Participants in efficacy cohorts were recruited between May 31 and Nov 13, 2020, and received booster doses between Aug 3 and Dec 30, 2020. Of 8534 participants in the primary efficacy cohort, 6636 (78%) were aged 18-55 years and 5065 (59%) were female. Between Oct 1, 2020, and Jan 14, 2021, 520 participants developed SARS-CoV-2 infection. 1466 NAAT positive nose and throat swabs were collected from these participants during the trial. Of these, 401 swabs from 311 participants were successfully sequenced. Laboratory virus neutralisation activity by vaccine-induced antibodies was lower against the B.1.1.7 variant than against the Victoria lineage (geometric mean ratio 8·9, 95% CI 7·2-11·0). Clinical vaccine efficacy against symptomatic NAAT positive infection was 70·4% (95% CI 43·6-84·5) for B.1.1.7 and 81·5% (67·9-89·4) for non-B.1.1.7 lineages., Interpretation: ChAdOx1 nCoV-19 showed reduced neutralisation activity against the B.1.1.7 variant compared with a non-B.1.1.7 variant in vitro, but the vaccine showed efficacy against the B.1.1.7 variant of SARS-CoV-2., Funding: UK Research and Innovation, National Institute for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midlands NIHR Clinical Research Network, and AstraZeneca., Competing Interests: Declaration of interests Oxford University has entered into a partnership with AstraZeneca for further development of ChAdOx1 nCoV-19. AstraZeneca reviewed the data from the study and the final manuscript before submission but the authors retained editorial control. SCG is cofounder of Vaccitech (collaborators in the early development of this vaccine candidate) and is named as an inventor on a patent covering use of ChAdOx1-vectored vaccines (PCT/GB2012/000467) and a patent application covering this SARS-CoV-2 vaccine. TL is named as an inventor on a patent application covering this SARS-CoV-2 vaccine and was a consultant to Vaccitech. PMF is a consultant to Vaccitech. AJP is chair of the UK Department of Health and Social Care Joint Committee on Vaccination and Immunisation but does not participate in policy advice on coronavirus vaccines, and is a member of the WHO Strategic Advisory Group of Experts. AJP and SNF are NIHR senior investigators. AVSH is a cofounder of and consultant to Vaccitech and is named as an inventor on a patent covering design and use of ChAdOx1-vectored vaccines (PCT/GB2012/000467). MDS reports grants from Janssen, GlaxoSmithKline, Medimmune, Novavax, and MCM Vaccine, and grants and non-financial support from Pfizer outside of the submitted work. CMG reports personal fees from the Duke Human Vaccine Institute outside of the submitted work. ADD reports grants and personal fees from AstraZeneca outside of the submitted work. SNF reports grants from Janssen and Valneva outside of the submitted work. TLV and JV are employees of AstraZeneca. All other authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)
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48. Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials.
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Voysey M, Costa Clemens SA, Madhi SA, Weckx LY, Folegatti PM, Aley PK, Angus B, Baillie VL, Barnabas SL, Bhorat QE, Bibi S, Briner C, Cicconi P, Clutterbuck EA, Collins AM, Cutland CL, Darton TC, Dheda K, Dold C, Duncan CJA, Emary KRW, Ewer KJ, Flaxman A, Fairlie L, Faust SN, Feng S, Ferreira DM, Finn A, Galiza E, Goodman AL, Green CM, Green CA, Greenland M, Hill C, Hill HC, Hirsch I, Izu A, Jenkin D, Joe CCD, Kerridge S, Koen A, Kwatra G, Lazarus R, Libri V, Lillie PJ, Marchevsky NG, Marshall RP, Mendes AVA, Milan EP, Minassian AM, McGregor A, Mujadidi YF, Nana A, Padayachee SD, Phillips DJ, Pittella A, Plested E, Pollock KM, Ramasamy MN, Ritchie AJ, Robinson H, Schwarzbold AV, Smith A, Song R, Snape MD, Sprinz E, Sutherland RK, Thomson EC, Török ME, Toshner M, Turner DPJ, Vekemans J, Villafana TL, White T, Williams CJ, Douglas AD, Hill AVS, Lambe T, Gilbert SC, and Pollard AJ
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- Adolescent, Adult, Aged, Antibody Formation, Asymptomatic Infections, COVID-19 Vaccines adverse effects, ChAdOx1 nCoV-19, Humans, Middle Aged, Randomized Controlled Trials as Topic, SARS-CoV-2 immunology, Young Adult, COVID-19 prevention & control, COVID-19 Vaccines administration & dosage, COVID-19 Vaccines immunology, Immunization Schedule, Immunization, Secondary
- Abstract
Background: The ChAdOx1 nCoV-19 (AZD1222) vaccine has been approved for emergency use by the UK regulatory authority, Medicines and Healthcare products Regulatory Agency, with a regimen of two standard doses given with an interval of 4-12 weeks. The planned roll-out in the UK will involve vaccinating people in high-risk categories with their first dose immediately, and delivering the second dose 12 weeks later. Here, we provide both a further prespecified pooled analysis of trials of ChAdOx1 nCoV-19 and exploratory analyses of the impact on immunogenicity and efficacy of extending the interval between priming and booster doses. In addition, we show the immunogenicity and protection afforded by the first dose, before a booster dose has been offered., Methods: We present data from three single-blind randomised controlled trials-one phase 1/2 study in the UK (COV001), one phase 2/3 study in the UK (COV002), and a phase 3 study in Brazil (COV003)-and one double-blind phase 1/2 study in South Africa (COV005). As previously described, individuals 18 years and older were randomly assigned 1:1 to receive two standard doses of ChAdOx1 nCoV-19 (5 × 10
10 viral particles) or a control vaccine or saline placebo. In the UK trial, a subset of participants received a lower dose (2·2 × 1010 viral particles) of the ChAdOx1 nCoV-19 for the first dose. The primary outcome was virologically confirmed symptomatic COVID-19 disease, defined as a nucleic acid amplification test (NAAT)-positive swab combined with at least one qualifying symptom (fever ≥37·8°C, cough, shortness of breath, or anosmia or ageusia) more than 14 days after the second dose. Secondary efficacy analyses included cases occuring at least 22 days after the first dose. Antibody responses measured by immunoassay and by pseudovirus neutralisation were exploratory outcomes. All cases of COVID-19 with a NAAT-positive swab were adjudicated for inclusion in the analysis by a masked independent endpoint review committee. The primary analysis included all participants who were SARS-CoV-2 N protein seronegative at baseline, had had at least 14 days of follow-up after the second dose, and had no evidence of previous SARS-CoV-2 infection from NAAT swabs. Safety was assessed in all participants who received at least one dose. The four trials are registered at ISRCTN89951424 (COV003) and ClinicalTrials.gov, NCT04324606 (COV001), NCT04400838 (COV002), and NCT04444674 (COV005)., Findings: Between April 23 and Dec 6, 2020, 24 422 participants were recruited and vaccinated across the four studies, of whom 17 178 were included in the primary analysis (8597 receiving ChAdOx1 nCoV-19 and 8581 receiving control vaccine). The data cutoff for these analyses was Dec 7, 2020. 332 NAAT-positive infections met the primary endpoint of symptomatic infection more than 14 days after the second dose. Overall vaccine efficacy more than 14 days after the second dose was 66·7% (95% CI 57·4-74·0), with 84 (1·0%) cases in the 8597 participants in the ChAdOx1 nCoV-19 group and 248 (2·9%) in the 8581 participants in the control group. There were no hospital admissions for COVID-19 in the ChAdOx1 nCoV-19 group after the initial 21-day exclusion period, and 15 in the control group. 108 (0·9%) of 12 282 participants in the ChAdOx1 nCoV-19 group and 127 (1·1%) of 11 962 participants in the control group had serious adverse events. There were seven deaths considered unrelated to vaccination (two in the ChAdOx1 nCov-19 group and five in the control group), including one COVID-19-related death in one participant in the control group. Exploratory analyses showed that vaccine efficacy after a single standard dose of vaccine from day 22 to day 90 after vaccination was 76·0% (59·3-85·9). Our modelling analysis indicated that protection did not wane during this initial 3-month period. Similarly, antibody levels were maintained during this period with minimal waning by day 90 (geometric mean ratio [GMR] 0·66 [95% CI 0·59-0·74]). In the participants who received two standard doses, after the second dose, efficacy was higher in those with a longer prime-boost interval (vaccine efficacy 81·3% [95% CI 60·3-91·2] at ≥12 weeks) than in those with a short interval (vaccine efficacy 55·1% [33·0-69·9] at <6 weeks). These observations are supported by immunogenicity data that showed binding antibody responses more than two-fold higher after an interval of 12 or more weeks compared with an interval of less than 6 weeks in those who were aged 18-55 years (GMR 2·32 [2·01-2·68])., Interpretation: The results of this primary analysis of two doses of ChAdOx1 nCoV-19 were consistent with those seen in the interim analysis of the trials and confirm that the vaccine is efficacious, with results varying by dose interval in exploratory analyses. A 3-month dose interval might have advantages over a programme with a short dose interval for roll-out of a pandemic vaccine to protect the largest number of individuals in the population as early as possible when supplies are scarce, while also improving protection after receiving a second dose., Funding: UK Research and Innovation, National Institutes of Health Research (NIHR), The Coalition for Epidemic Preparedness Innovations, the Bill & Melinda Gates Foundation, the Lemann Foundation, Rede D'Or, the Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)- Published
- 2021
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49. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.
- Author
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Voysey M, Clemens SAC, Madhi SA, Weckx LY, Folegatti PM, Aley PK, Angus B, Baillie VL, Barnabas SL, Bhorat QE, Bibi S, Briner C, Cicconi P, Collins AM, Colin-Jones R, Cutland CL, Darton TC, Dheda K, Duncan CJA, Emary KRW, Ewer KJ, Fairlie L, Faust SN, Feng S, Ferreira DM, Finn A, Goodman AL, Green CM, Green CA, Heath PT, Hill C, Hill H, Hirsch I, Hodgson SHC, Izu A, Jackson S, Jenkin D, Joe CCD, Kerridge S, Koen A, Kwatra G, Lazarus R, Lawrie AM, Lelliott A, Libri V, Lillie PJ, Mallory R, Mendes AVA, Milan EP, Minassian AM, McGregor A, Morrison H, Mujadidi YF, Nana A, O'Reilly PJ, Padayachee SD, Pittella A, Plested E, Pollock KM, Ramasamy MN, Rhead S, Schwarzbold AV, Singh N, Smith A, Song R, Snape MD, Sprinz E, Sutherland RK, Tarrant R, Thomson EC, Török ME, Toshner M, Turner DPJ, Vekemans J, Villafana TL, Watson MEE, Williams CJ, Douglas AD, Hill AVS, Lambe T, Gilbert SC, and Pollard AJ
- Subjects
- Adolescent, Adult, Aged, Brazil, ChAdOx1 nCoV-19, Double-Blind Method, Female, Humans, Male, Middle Aged, Single-Blind Method, South Africa, Treatment Outcome, United Kingdom, Young Adult, COVID-19 prevention & control, COVID-19 Vaccines adverse effects
- Abstract
Background: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials., Methods: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 10
10 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674., Findings: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction =0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation., Interpretation: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials., Funding: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)- Published
- 2021
- Full Text
- View/download PDF
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