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1. A systematic analysis of the human immune response to Plasmodium vivax

Author

Bach, Florian A., Sandoval, Diana Munoz, Mazurczyk, Michalina, Themistocleous, Yrene, Rawlinson, Thomas A., Harding, Adam C., Kemp, Alison, Silk, Sarah E., Barrett, Jordan R., Edwards, Nick J., Ivens, Alasdair, Rayner, Julian C., Minassian, Angela M., Napolitani, Giorgio, Draper, Simon J., and Spence, Philip J.

Subjects
Interferon -- Comparative analysis -- Health aspects, Medical research -- Comparative analysis -- Health aspects, Medicine, Experimental -- Comparative analysis -- Health aspects, T cells -- Comparative analysis -- Health aspects, RNA sequencing -- Health aspects -- Comparative analysis, Immune response -- Health aspects -- Comparative analysis, Biological response modifiers -- Comparative analysis -- Health aspects, Infection -- Comparative analysis -- Health aspects, Malaria -- Health aspects -- Comparative analysis, RNA -- Health aspects -- Comparative analysis, Cell differentiation -- Comparative analysis -- Health aspects, Plasmodium falciparum -- Comparative analysis -- Health aspects, Health care industry, Wellcome Trust
Abstract

BACKGROUND. The biology of Plasmodium vivax is markedly different from that of P. falciparum; how this shapes the immune response to infection remains unclear. To address this shortfall, we inoculated human volunteers with a clonal field isolate of P. vivax and tracked their response through infection and convalescence. METHODS. Participants were injected intravenously with blood-stage parasites and infection dynamics were tracked in real time by quantitative PCR. Whole blood samples were used for high dimensional protein analysis, RNA sequencing, and cytometry by time of flight, and temporal changes in the host response to P. vivax were quantified by linear regression. Comparative analyses with P. falciparum were then undertaken using analogous data sets derived from prior controlled human malaria infection studies. RESULTS. P. vivax rapidly induced a type I inflammatory response that coincided with hallmark features of clinical malaria. This acute-phase response shared remarkable overlap with that induced by P. falciparum but was significantly elevated (at RNA and protein levels), leading to an increased incidence of pyrexia. In contrast, T cell activation and terminal differentiation were significantly increased in volunteers infected with P. falciparum. Heterogeneous [CD4.sup.+] T cells were found to dominate this adaptive response and phenotypic analysis revealed unexpected features normally associated with cytotoxicity and autoinflammatory disease. CONCLUSION. P. vivax triggers increased systemic interferon signaling (cf P. falciparum), which likely explains its reduced pyrogenic threshold. In contrast, P. falciparum drives T cell activation far in excess of P. vivax, which may partially explain why falciparum malaria more frequently causes severe disease. TRIAL REGISTRATION. ClinicalTrials.gov NCT03797989. FUNDING. The European Union's Horizon 2020 Research and Innovation programme, the Wellcome Trust, and the Royal Society., Introduction Plasmodium vivax causes more than half of all malaria cases in the Americas and Southeast Asia (1) and its distinct biology (cf P falciparum) presents unique challenges for control [...]

Published
2023
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2. Towards an effective vaccine against Plasmodium vivax malaria

Author

Rawlinson, Thomas, Draper, Simon, and Higgins, Matt

Subjects
616.9
Abstract

Over seventy vaccines are now licensed against more than thirty pathogens, but despite a century of effort, the malaria parasite is not among them. In the meantime, effective drugs and anti-mosquito measures notwithstanding, millions still suffer and die from of a disease which belongs in the history books. The reasons are largely political and economic, malaria is a neglected disease of the poor, but also scientific; a parasite as protean as Plasmodium is not easy to pin down with a vaccine. It has been known for over a hundred years that almost a billion people on the world's most malarial continent are 'naturally immune' to Plasmodium vivax (P. vivax) malaria. I can think of no other human pathogen with such an ancient and continental-scale natural experiment to inspire research. The source of this immunity was discovered, over forty years ago, to be due to the lack of the Duffy antigen on the surface of red blood cells. The parasite must bind to this Duffy antigen, using its 'Duffy-binding protein' (DBP), in order to invade the erythrocyte. Despite this 'Achilles heel' of P. vivax being known about for decades, it was not until 2014 that it was first targeted in a human vaccine trial. This long overdue trial of a P. vivax DBP (PvDBP) vaccine provided the source material for, and the starting point of, this DPhil Thesis. The extreme polymorphism of malaria antigens, such as PvDBP, poses a great challenge to vaccine design, but new approaches are emerging to tackle this and it is one of these, known as 'epitope-focused vaccinology', that I pursue in this Thesis. I report the production of the first panel of vaccine-induced human monoclonal antibodies (mAb) against PvDBP and, through testing in functional assays using both P. vivax and a transgenic Plasmodium knowlesi line, the discovery of a broadly-neutralising mAb. X-ray crystallographic studies have identified its epitope on PvDBP and the process of re-engineering the PvDBP vaccine to place this conserved and critical epitope in the immune system's spotlight has begun.

Published
2018

3. Reduced blood-stage malaria growth and immune correlates in humans following RH5 vaccination

Author

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.

Published
2021
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4. A Humanized Mouse Model for Plasmodium vivax to Test Interventions that Block Liver Stage to Blood Stage Transition and Blood Stage Infection

Author

Schäfer, Carola, Roobsoong, Wanlapa, Kangwanrangsan, Niwat, Bardelli, Martino, Rawlinson, Thomas A., Dambrauskas, Nicholas, Trakhimets, Olesya, Parthiban, Chaitra, Goswami, Debashree, Reynolds, Laura M., Kennedy, Spencer Y., Flannery, Erika L., Murphy, Sean C., Sather, D. Noah, Draper, Simon J., Sattabongkot, Jetsumon, Mikolajczak, Sebastian A., and Kappe, Stefan H.I.

Published
2020
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5. Structural basis for inhibition of Plasmodium vivax invasion by a broadly neutralizing vaccine-induced human antibody

Author

Rawlinson, Thomas. A., Barber, Natalie M., Mohring, Franziska, Cho, Jee Sun, Kosaisavee, Varakorn, Gérard, Samuel F., Alanine, Daniel G. W., Labbé, Geneviève M., Elias, Sean C., Silk, Sarah E., Quinkert, Doris, Jin, Jing, Marshall, Jennifer M., Payne, Ruth O., Minassian, Angela M., Russell, Bruce, Rénia, Laurent, Nosten, François H., Moon, Robert W., Higgins, Matthew K., and Draper, Simon J.

Published
2019
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6. Vaccination with Plasmodium vivax Duffy-binding protein inhibits parasite growth during controlled human malaria infection

Author

Hou, Mimi M., primary, Barrett, Jordan R., additional, Themistocleous, Yrene, additional, Rawlinson, Thomas A., additional, Diouf, Ababacar, additional, Martinez, Francisco J., additional, Nielsen, Carolyn M., additional, Lias, Amelia M., additional, King, Lloyd D. W., additional, Edwards, Nick J., additional, Greenwood, Nicola M., additional, Kingham, Lucy, additional, Poulton, Ian D., additional, Khozoee, Baktash, additional, Goh, Cyndi, additional, Hodgson, Susanne H., additional, Mac Lochlainn, Dylan J., additional, Salkeld, Jo, additional, Guillotte-Blisnick, Micheline, additional, Huon, Christèle, additional, Mohring, Franziska, additional, Reimer, Jenny M., additional, Chauhan, Virander S., additional, Mukherjee, Paushali, additional, Biswas, Sumi, additional, Taylor, Iona J., additional, Lawrie, Alison M., additional, Cho, Jee-Sun, additional, Nugent, Fay L., additional, Long, Carole A., additional, Moon, Robert W., additional, Miura, Kazutoyo, additional, Silk, Sarah E., additional, Chitnis, Chetan E., additional, Minassian, Angela M., additional, and Draper, Simon J., additional

Published
2023
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8. Repeat controlled human malaria infection of healthy UK adults with blood-stage Plasmodium falciparum: Safety and parasite growth dynamics

Author

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

Published
2022
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9. Repeat controlled human malaria infection of healthy UK adults with blood-stagePlasmodium falciparum: safety and parasite growth dynamics

Author

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

Published
2022
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10. Impact of a blood-stage vaccine on Plasmodium vivax malaria

Author

Hou, Mimi M., primary, Barrett, Jordan R., additional, Themistocleous, Yrene, additional, Rawlinson, Thomas A., additional, Diouf, Ababacar, additional, Martinez, Francisco J., additional, Nielsen, Carolyn M., additional, Lias, Amelia M., additional, King, Lloyd D. W., additional, Edwards, Nick J., additional, Greenwood, Nicola M., additional, Kingham, Lucy, additional, Poulton, Ian D., additional, Khozoee, Baktash, additional, Goh, Cyndi, additional, Mac Lochlainn, Dylan J., additional, Salkeld, Jo, additional, Guilotte-Blisnick, Micheline, additional, Huon, Christèle, additional, Mohring, Franziska, additional, Reimer, Jenny M., additional, Chauhan, Virander S., additional, Mukherjee, Paushali, additional, Biswas, Sumi, additional, Taylor, Iona J., additional, Lawrie, Alison M., additional, Cho, Jee-Sun, additional, Nugent, Fay L., additional, Long, Carole A., additional, Moon, Robert W., additional, Miura, Kazutoyo, additional, Silk, Sarah E., additional, Chitnis, Chetan E., additional, Minassian, Angela M., additional, and Draper, Simon J., additional

Published
2022
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11. Controlled human malaria infection with a clone of Plasmodium vivax with high-quality genome assembly

Author

Minassian, Angela M., primary, Themistocleous, Yrene, additional, Silk, Sarah E., additional, Barrett, Jordan R., additional, Kemp, Alison, additional, Quinkert, Doris, additional, Nielsen, Carolyn M., additional, Edwards, Nick J., additional, Rawlinson, Thomas A., additional, Ramos Lopez, Fernando, additional, Roobsoong, Wanlapa, additional, Ellis, Katherine J.D., additional, Cho, Jee-Sun, additional, Aunin, Eerik, additional, Otto, Thomas D., additional, Reid, Adam J., additional, Bach, Florian A., additional, Labbé, Geneviève M.C., additional, Poulton, Ian D., additional, Marini, Arianna, additional, Zaric, Marija, additional, Mulatier, Margaux, additional, Lopez Ramon, Raquel, additional, Baker, Megan, additional, Mitton, Celia H., additional, Sousa, Jason C., additional, Rachaphaew, Nattawan, additional, Kumpitak, Chalermpon, additional, Maneechai, Nongnuj, additional, Suansomjit, Chayanut, additional, Piteekan, Tianrat, additional, Hou, Mimi M., additional, Khozoee, Baktash, additional, McHugh, Kirsty, additional, Roberts, David J., additional, Lawrie, Alison M., additional, Blagborough, Andrew M., additional, Nugent, Fay L., additional, Taylor, Iona J., additional, Johnson, Kimberly J., additional, Spence, Philip J., additional, Sattabongkot, Jetsumon, additional, Biswas, Sumi, additional, Rayner, Julian C., additional, and Draper, Simon J., additional

Published
2021
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12. PAPERS IN AGRICULTURE

Author

Kilderbee, Samuel, More, Samuel, Denny, John, Browne, William, Berrett, Robert, Downing, Wiilliam, Bird, Thomas, Edis, William, MORE, Todd, William, Edwards, Samuel, Phillips, J., Tansley, Henry, Crawley, Samuel, Calvert, William, Nevill, George, Chapman, William, Rawlinson, Thomas, Horrabin, Richard, Bucknall, Thomas Skip Dyot, Hampson, William, Torrington, Hugh, Pulman, John, Wood, James, Harper, Henry, Heathcote, Henry, Holt, John, Jenkinson, John, Ford, John, Middleton, John, Bramley, Richard Ramsden, Lockett, John, and Randall, William

Published
1795

13. Controlled human malaria infection with PvW1 – a new clone of Plasmodium vivax with high quality genome assembly

Author

Minassian, Angela M., primary, Themistocleous, Yrene, additional, Silk, Sarah E., additional, Barrett, Jordan R., additional, Kemp, Alison, additional, Quinkert, Doris, additional, Nielsen, Carolyn M., additional, Edwards, Nick J., additional, Rawlinson, Thomas A., additional, Lopez, Fernando Ramos, additional, Roobsoong, Wanlapa, additional, Ellis, Katherine J., additional, Cho, Jee-Sun, additional, Aunin, Eerik, additional, Otto, Thomas D., additional, Reid, Adam J., additional, Bach, Florian, additional, Labbé, Geneviève M., additional, Poulton, Ian D., additional, Marini, Arianna, additional, Zaric, Marija, additional, Mulatier, Margaux, additional, Ramon, Raquel Lopez, additional, Baker, Megan, additional, Mitton, Celia H., additional, Sousa, Jason C., additional, Rachaphaew, Nattawan, additional, Kumpitak, Chalermpon, additional, Maneechai, Nongnuj, additional, Suansomjit, Chayanut, additional, Piteekan, Tianrat, additional, Hou, Mimi M., additional, Khozoee, Baktash, additional, Roberts, David J., additional, Lawrie, Alison M., additional, Blagborough, Andrew M., additional, Nugent, Fay L., additional, Taylor, Iona J., additional, Johnson, Kimberly J., additional, Spence, Philip J., additional, Sattabongkot, Jetsumon, additional, Biswas, Sumi, additional, Rayner, Julian C., additional, and Draper, Simon J., additional

Published
2021
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14. T cell and antibody responses induced by a single dose of ChAdOx1 nCoV-19 (AZD1222) vaccine in a phase 1/2 clinical trial

Author

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

Subjects
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.

Published
2020
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15. Mapping T cell activation and differentiation at single cell resolution in naive hosts infected withPlasmodium vivax

Author

Bach, Florian A., primary, Muñoz Sandoval, Diana, additional, Mazurczyk, Michalina, additional, Themistocleous, Yrene, additional, Rawlinson, Thomas A., additional, Kemp, Alison, additional, Silk, Sarah E., additional, Barrett, Jordan R., additional, Edwards, Nick J., additional, Ivens, Alasdair, additional, Rayner, Julian C., additional, Minassian, Angela M., additional, Napolitani, Giorgio, additional, Draper, Simon J., additional, and Spence, Philip J., additional

Published
2021
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16. 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

Author

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

Published
2020
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24. 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

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

Published
2020
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28. Rapid and iterative genome editing in the malaria parasite Plasmodium knowlesi provides new tools for P. vivax research

Author

Mohring, Franziska, primary, Hart, Melissa Natalie, additional, Rawlinson, Thomas A, additional, Henrici, Ryan, additional, Charleston, James A, additional, Diez Benavente, Ernest, additional, Patel, Avnish, additional, Hall, Joanna, additional, Almond, Neil, additional, Campino, Susana, additional, Clark, Taane G, additional, Sutherland, Colin J, additional, Baker, David A, additional, Draper, Simon J, additional, and Moon, Robert William, additional

Published
2019
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29. Divergent roles for the RH5 complex components, CyRPA and RIPR in human-infective malaria parasites

Author

Knuepfer, Ellen, primary, Wright, Katherine E., additional, Kumar Prajapati, Surendra, additional, Rawlinson, Thomas A., additional, Mohring, Franziska, additional, Koch, Marion, additional, Lyth, Oliver R., additional, Howell, Steven A., additional, Villasis, Elizabeth, additional, Snijders, Ambrosius P., additional, Moon, Robert W., additional, Draper, Simon J., additional, Rosanas-Urgell, Anna, additional, Higgins, Matthew K., additional, Baum, Jake, additional, and Holder, Anthony A., additional

Published
2019
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30. Author response: Rapid and iterative genome editing in the malaria parasite Plasmodium knowlesi provides new tools for P. vivax research

Author

Mohring, Franziska, primary, Hart, Melissa Natalie, additional, Rawlinson, Thomas A, additional, Henrici, Ryan, additional, Charleston, James A, additional, Diez Benavente, Ernest, additional, Patel, Avnish, additional, Hall, Joanna, additional, Almond, Neil, additional, Campino, Susana, additional, Clark, Taane G, additional, Sutherland, Colin J, additional, Baker, David A, additional, Draper, Simon J, additional, and Moon, Robert William, additional

Published
2019
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31. Rapid and iterative genome editing in the zoonotic malaria parasitePlasmodium knowlesi: New tools forP. vivaxresearch

Author

Mohring, Franziska, primary, Hart, Melissa N., additional, Rawlinson, Thomas A., additional, Henrici, Ryan, additional, Charleston, James A., additional, Benavente, Ernest Diez, additional, Patel, Avnish, additional, Hall, Joanna, additional, Almond, Neil, additional, Campino, Susana, additional, Clark, Taane G., additional, Sutherland, Colin J., additional, Baker, David A., additional, Draper, Simon J., additional, and Moon, Robert W., additional

Published
2019
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32. Human vaccination against Plasmodium vivax Duffy-binding protein induces strain-transcending antibodies

Author

Payne, Ruth O., primary, Silk, Sarah E., additional, Elias, Sean C., additional, Milne, Kathryn H., additional, Rawlinson, Thomas A., additional, Llewellyn, David, additional, Shakri, A. Rushdi, additional, Jin, Jing, additional, Labbé, Geneviève M., additional, Edwards, Nick J., additional, Poulton, Ian D., additional, Roberts, Rachel, additional, Farid, Ryan, additional, Jørgensen, Thomas, additional, Alanine, Daniel G.W., additional, de Cassan, Simone C., additional, Higgins, Matthew K., additional, Otto, Thomas D., additional, McCarthy, James S., additional, de Jongh, Willem A., additional, Nicosia, Alfredo, additional, Moyle, Sarah, additional, Hill, Adrian V.S., additional, Berrie, Eleanor, additional, Chitnis, Chetan E., additional, Lawrie, Alison M., additional, and Draper, Simon J., additional

Published
2017
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33. Vaccination with Plasmodium vivaxDuffy-binding protein inhibits parasite growth during controlled human malaria infection

Author

Hou, Mimi M., Barrett, Jordan R., Themistocleous, Yrene, Rawlinson, Thomas A., Diouf, Ababacar, Martinez, Francisco J., Nielsen, Carolyn M., Lias, Amelia M., King, Lloyd D. W., Edwards, Nick J., Greenwood, Nicola M., Kingham, Lucy, Poulton, Ian D., Khozoee, Baktash, Goh, Cyndi, Hodgson, Susanne H., Mac Lochlainn, Dylan J., Salkeld, Jo, Guillotte-Blisnick, Micheline, Huon, Christèle, Mohring, Franziska, Reimer, Jenny M., Chauhan, Virander S., Mukherjee, Paushali, Biswas, Sumi, Taylor, Iona J., Lawrie, Alison M., Cho, Jee-Sun, Nugent, Fay L., Long, Carole A., Moon, Robert W., Miura, Kazutoyo, Silk, Sarah E., Chitnis, Chetan E., Minassian, Angela M., and Draper, Simon J.

Abstract

There are no licensed vaccines against Plasmodium vivax. We conducted two phase 1/2a clinical trials to assess two vaccines targeting P. vivaxDuffy-binding protein region II (PvDBPII). Recombinant viral vaccines using chimpanzee adenovirus 63 (ChAd63) and modified vaccinia virus Ankara (MVA) vectors as well as a protein and adjuvant formulation (PvDBPII/Matrix-M) were tested in both a standard and a delayed dosing regimen. Volunteers underwent controlled human malaria infection (CHMI) after their last vaccination, alongside unvaccinated controls. Efficacy was assessed by comparisons of parasite multiplication rates in the blood. PvDBPII/Matrix-M, given in a delayed dosing regimen, elicited the highest antibody responses and reduced the mean parasite multiplication rate after CHMI by 51% (n= 6) compared with unvaccinated controls (n= 13), whereas no other vaccine or regimen affected parasite growth. Both viral-vectored and protein vaccines were well tolerated and elicited expected, short-lived adverse events. Together, these results support further clinical evaluation of the PvDBPII/Matrix-M P. vivaxvaccine.

Published
2023
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34. Light sown for the righteous, and gladness for the upright in heart. This is to go abroad among all people who are honest-hearted, especially amongst the inhabitants in Fourns Fells, in Lancashire, and among all who have known me after the flesh, that all honest people may see what I was in profession, and also what I now am by the grace of God. From him which hath come through great tribulations, who hath even left all for Christ, and hath not whereon to lay his head, but is forsaken of father and of mother, and of kinred also, even for the testimony of Jesus, and for the Word of God, whom the world calls, Thomas Rawlinson.

Author

Rawlinson, Thomas., Rawlinson, Thomas., Rawlinson, Thomas., and Rawlinson, Thomas.

Abstract

[2], 37, [1] p., Caption title on p. 1 reads: This is to go abroad into my countrey, amongst the inhabitants in Fornes Fells, and among all honest people that have known me after the flesh, that all people may see what I was in profession, and what I now am by the grace of God., Reproduction of the original in the John Rylands University Library of Manchester., (marc) 99831963, (stc) Wing (2nd ed.) R369., http://quod.lib.umich.edu/t/text/accesspolicy.html

35. Light sown for the righteous, and gladness for the upright in heart. This is to go abroad among all people who are honest-hearted, especially amongst the inhabitants in Fourns Fells, in Lancashire, and among all who have known me after the flesh, that all honest people may see what I was in profession, and also what I now am by the grace of God. From him which hath come through great tribulations, who hath even left all for Christ, and hath not whereon to lay his head, but is forsaken of father and of mother, and of kinred also, even for the testimony of Jesus, and for the Word of God, whom the world calls, Thomas Rawlinson.

Author

Rawlinson, Thomas., Rawlinson, Thomas., Rawlinson, Thomas., and Rawlinson, Thomas.

Abstract

[2], 37, [1] p., Caption title on p. 1 reads: This is to go abroad into my countrey, amongst the inhabitants in Fornes Fells, and among all honest people that have known me after the flesh, that all people may see what I was in profession, and what I now am by the grace of God., Reproduction of the original in the John Rylands University Library of Manchester., (marc) 99831963, (stc) Wing (2nd ed.) R369., http://quod.lib.umich.edu/t/text/accesspolicy.html

36. Divergent roles for the RH5 complex components, CyRPA and RIPR, in human-infective malaria parasites

Author

Knuepfer, Ellen, Wright, Katherine E, Surendra Kumar Prajapati, Rawlinson, Thomas A, Mohring, Franziska, Koch, Marion, Lyth, Oliver R, Howell, Steven A, Villasis, Elizabeth, Snijders, Ambrosius P, Moon, Robert W, Draper, Simon J, Rosanans-Urgell, Anna, Higgins, Matthew K, Baum, Jake, and Holder, Anthony A

Subjects
Model organisms, Chemical Biology & High Throughput, parasitic diseases, Infectious Disease, Cell Biology, Biochemistry & Proteomics, 3. Good health, Computational & Systems Biology
Abstract

Malaria is caused by Plasmodium parasites, which invade and replicate in erythrocytes. For Plasmodium falciparum, the major cause of severe malaria in humans, a heterotrimeric complex comprised of the secreted parasite proteins, PfCyRPA, PfRIPR and PfRH5 is essential for erythrocyte invasion, mediated by the interaction between PfRH5 and erythrocyte receptor basigin (BSG). However, whilst CyRPA and RIPR are present in most Plasmodium species, RH5 is found only in the small Laverania subgenus. Existence of a complex analogous to PfRH5-PfCyRPA-PfRIPR targeting BSG, and involvement of CyRPA and RIPR in invasion, however, has not been addressed in non-Laverania parasites. Here, we establish that unlike P. falciparum, P. knowlesi and P. vivax do not universally require BSG as a host cell invasion receptor. Although we show that both PkCyRPA and PkRIPR are essential for successful invasion of erythrocytes by P. knowlesi parasites in vitro, neither protein forms a complex with each other or with an RH5-like molecule. Instead, PkRIPR is part of a different trimeric protein complex whereas PkCyRPA appears to function without other parasite binding partners. It therefore appears that in the absence of RH5, outside of the Laverania subgenus, RIPR and CyRPA have different, independent functions crucial for parasite survival.

38. Impact of a blood-stage vaccine on Plasmodium vivax malaria.

Author

Hou MM, Barrett JR, Themistocleous Y, Rawlinson TA, Diouf A, Martinez FJ, Nielsen CM, Lias AM, King LDW, Edwards NJ, Greenwood NM, Kingham L, Poulton ID, Khozoee B, Goh C, Mac Lochlainn DJ, Salkeld J, Guilotte-Blisnick M, Huon C, Mohring F, Reimer JM, Chauhan VS, Mukherjee P, Biswas S, Taylor IJ, Lawrie AM, Cho JS, Nugent FL, Long CA, Moon RW, Miura K, Silk SE, Chitnis CE, Minassian AM, and Draper SJ

Abstract

Background: There are no licensed vaccines against Plasmodium vivax , the most common cause of malaria outside of Africa., Methods: We conducted two Phase I/IIa clinical trials to assess the safety, immunogenicity and efficacy of two vaccines targeting region II of P. vivax Duffy-binding protein (PvDBPII). Recombinant viral vaccines (using ChAd63 and MVA vectors) were administered at 0, 2 months or in a delayed dosing regimen (0, 17, 19 months), whilst a protein/adjuvant formulation (PvDBPII/Matrix-M™) was administered monthly (0, 1, 2 months) or in a delayed dosing regimen (0, 1, 14 months). Delayed regimens were due to trial halts during the COVID-19 pandemic. Volunteers underwent heterologous controlled human malaria infection (CHMI) with blood-stage P. vivax parasites at 2-4 weeks following their last vaccination, alongside unvaccinated controls. Efficacy was assessed by comparison of parasite multiplication rate (PMR) in blood post-CHMI, modelled from parasitemia measured by quantitative polymerase-chain-reaction (qPCR)., Results: Thirty-two volunteers were enrolled and vaccinated (n=16 for each vaccine). No safety concerns were identified. PvDBPII/Matrix-M™, given in the delayed dosing regimen, elicited the highest antibody responses and reduced the mean PMR following CHMI by 51% (range 36-66%; n=6) compared to unvaccinated controls (n=13). No other vaccine or regimen impacted parasite growth. In vivo growth inhibition of blood-stage P. vivax correlated with functional antibody readouts of vaccine immunogenicity., Conclusions: Vaccination of malaria-naïve adults with a delayed booster regimen of PvDBPII/ Matrix-M™ significantly reduces the growth of blood-stage P. vivax . Funded by the European Commission and Wellcome Trust; VAC069, VAC071 and VAC079 ClinicalTrials.gov numbers NCT03797989 , NCT04009096 and NCT04201431 .

Published
2022
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39. 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.

Author

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

Subjects
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 × 10 10 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 (MNA 80 ). 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 MNA 80 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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