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2. 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, Alderson, Jennifer, Bittaye, Mustapha, Dold, Christina, Provine, Nicholas M., Aboagye, Jeremy, Fowler, Jamie, Silk, Sarah E., Aley, Parvinder K., Bellamy, Duncan, and Wright, Daniel

Subjects
T cells -- Physiological aspects, Biological sciences, Health
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 needed.sup.1. Strong, Th1-skewed T cell responses can drive protective humoral and cell-mediated immune responses.sup.2 and might reduce the potential for disease enhancement.sup.3. Cytotoxic T cells clear virus-infected host cells and contribute to control of infection.sup.4. 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. .sup.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).sup.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-[gamma] and tumor necrosis factor-[alpha] cytokine secretion by CD4.sup.+ T cells and antibody production predominantly of IgG1 and IgG3 subclasses. CD8.sup.+ 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., Author(s): Katie J. Ewer [sup.1] , Jordan R. Barrett [sup.1] , Sandra Belij-Rammerstorfer [sup.1] , Hannah Sharpe [sup.1] , Rebecca Makinson [sup.1] , Richard Morter [sup.1] , Amy Flaxman [sup.1] [...]

Published
2021
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3. The Effect of Acute Knee Injuries and Related Knee Surgery on Serum Levels of Pro- and Anti-inflammatory Lipid Mediators and Their Associations With Knee Symptoms.

Author

Turnbull, James, Jha, Rakesh R., Barrett, David A., Valdes, Ana M., Alderson, Jennifer, Williams, Andrew, Vincent, Tonia L., Watt, Fiona E., and Chapman, Victoria

Subjects
KNEE osteoarthritis, DOCOSAHEXAENOIC acid, CROSS-sectional method, HYDROLASES, ANTI-inflammatory agents, INFLAMMATORY mediators, LIQUID chromatography-mass spectrometry, LIPIDS, OMEGA-3 fatty acids, EICOSAPENTAENOIC acid, LEUKOTRIENES, UNSATURATED fatty acids, LONGITUDINAL method, THROMBOXANES, PROSTAGLANDINS, COMPARATIVE studies, KNEE injuries, KNEE surgery, BIOMARKERS
Abstract

Background: Despite an acute knee injury being a major risk factor for osteoarthritis, the factors that initiate and maintain this risk of longer-term knee symptoms are poorly understood. Bioactive lipids derived from omega-3 and -6 polyunsaturated fatty acids have key roles in the regulation of the inflammatory response and have been linked to joint damage and osteoarthritis pain in translational models. Hypothesis: There would be associations between systemic levels of bioactive lipids and knee symptoms longitudinally after an acute knee injury and related knee surgery. Study Design: Controlled laboratory study. Methods: This study analyzed a subset of young, active adults who had sustained an acute knee injury (recruited via a surgical care pathway) and healthy age- and sex-matched controls. Surgery, if performed, was conducted after the baseline serum sample was taken and before the 3-month and 2-year visits. Liquid chromatography–tandem mass spectrometry of 41 bioactive lipids was carried out in sera of (1) 47 injured participants (median age, 28 years) collected at baseline (median, 24 days after injury), 3 months, and 2 years, along with the Knee injury and Osteoarthritis Outcome Score, and (2) age- and sex-matched controls. Results: Levels of the omega-3 polyunsaturated fatty acids eicosapentaenoic acid (P ≤.0001) and docosahexaenoic acid (P ≤.0001) and the pro-resolving lipid mediators 17– and 14–hydroxydocosahexaenoic acid, and 18-hydroxyeicosapentaenoic acid were all significantly greater at baseline in injured participants compared with the later time points and also higher than in healthy controls (P =.0019 and P ≤.0001, respectively). Levels of pro-inflammatory prostaglandins E2 and D2, leukotriene B4, and thromboxane B2 were significantly lower at baseline compared with the later time points. Higher levels of 8,9–, 11,12–, and 14,15–dihydroxyeicosatrienoic acid (DHET) were cross-sectionally associated with more severe knee pain/symptoms according to the Knee injury and Osteoarthritis Outcome Score at 2 years (P =.0004, R 2 = 0.251; P =.0002, R 2 = 0.278; and P =.0012, R 2 = 0.214, respectively). Conclusion: The profile of pro-resolving versus pro-inflammatory lipids at baseline suggests an initial activation of pro-resolution pathways, followed by the later activation of pro-inflammatory pathways. Clinical Relevance: In this largely surgically managed cohort, the association of soluble epoxide hydrolase metabolites, the DHETs, with more severe knee symptoms at 2 years provides a rationale for further investigation into the role of this pathway in persisting knee symptoms in this population, including potential therapeutic strategies. [ABSTRACT FROM AUTHOR]

Published
2024
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6. The role and uses of antibodies in COVID-19 infections: a living review

Author

Scourfield, D Oliver, Reed, Sophie G, Quastel, Max, Alderson, Jennifer, Bart, Valentina M T, Teijeira Crespo, Alicia, Jones, Ruth, Pring, Ellie, Richter, Felix Clemens, Ahern, David J, Almuttaqi, Hannah, Alonzi, Dominic S, Alrubayyi, Aljawharah, Alsaleh, Ghada, Batchelor, Vicky, Bayliss, Rebecca, Berthold, Dorothée L, Bezbradica, Jelena S, Bharuchq, Tehmina, Borrmann, Helene, Borsa, Mariana, Borst, Rowie, Brun, Juliane, Burnell, Stephanie E A, Capitani, Lorenzo, Cavounidis, Athena, Chapman, Lucy, Chauveau, Anne, Cifuentes, Liliana, Codd, Amy Susan, Compeer, Ewoud Bernardus, Coveney, Clarissa, Cross, Amy, Danielli, Sara, Davies, Luke C, Dendrou, Calliope A, Dimonte, Sandra, Peter Durairaj, Ruban Rex, Dustin, Lynn B, Dyer, Arthur, Fielding, Ceri, Fischer, Fabian, Gallimore, Awen, Galloway, Sarah, Gammage, Anís, Gea-Mallorquí, Ester, Godkin, Andrew, Hanna, Stephanie Jean, Heuberger, Cornelia, Hulin-Curtis, Sarah, Issa, Fadi, Jones, Emma, Ladell, Kristin, Lauder, Sarah N, Liddiard, Kate, Ligoxygakis, Petros, Lu, Fangfang, MacLachlan, Bruce, Maleki-Toyserkani, Shayda, Mann, Elizabeth H, Marzeda, Anna M, James Matthews, Reginald, Mazet, Julie M, Milicic, Anita, Mitchell, Emma, Moon, Owen, Nguyen, Van Dien, OHanlon, Miriam, Eléonore Pavillet, Clara, Peppa, Dimitra, Pires, Ana, Pring, Eleanor, Reed, Sophie, Rehwinkel, Jan, Richmond, Niamh, Robinson, Alice J B, Rodrigues, Patrícia R S, Sabberwal, Pragati, Sami, Arvind, Peres, Raphael Sanches, Sattentau, Quentin, Schonfeldova, Barbora, Scourfield, David Oliver, Selvakumar, Tharini A, Shepherd, Freya R, Shorten, Cariad, Simon, Anna Katharina, Smith, Adrian L, Crespo, Alicia Teijeira, Tellier, Michael, Thornton, Emily, Uhl, Lion F K, van Grinsven, Erinke, Wann, Angus K T, Williams, Richard, Wilson, Joseph D, Zhou, Dingxi, Zhu, Zihan, and Consortium, Oxford-Cardiff COVID-19 Literature

Subjects
0301 basic medicine, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Review Article, Disease, 03 medical and health sciences, 0302 clinical medicine, Immunity, Pandemic, antibodies, Medicine, Infection control, biology, SARS-CoV-2, business.industry, COVID-19, General Medicine, vaccines, nanobodies, 030104 developmental biology, convalescent plasma, Immunology, biology.protein, AcademicSubjects/SCI00960, Antibody, business, long-term immunity, 030217 neurology & neurosurgery
Abstract

Coronavirus disease 2019 has generated a rapidly evolving field of research, with the global scientific community striving for solutions to the current pandemic. Characterizing humoral responses towards SARS-CoV-2, as well as closely related strains, will help determine whether antibodies are central to infection control, and aid the design of therapeutics and vaccine candidates. This review outlines the major aspects of SARS-CoV-2-specific antibody research to date, with a focus on the various prophylactic and therapeutic uses of antibodies to alleviate disease in addition to the potential of cross-reactive therapies and the implications of long-term immunity.

Published
2021

7. 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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9. Active immunisation targeting nerve growth factor attenuates chronic pain behaviour in murine osteoarthritis

Author

von Loga, Isabell S, El-Turabi, Aadil, Jostins, Luke, Miotla-Zarebska, Jadwiga, Mackay-Alderson, Jennifer, Zeltins, Andris, Parisi, Ida, Bachmann, Martin F, and Vincent, Tonia L

Subjects
Male, Analgesics, Vaccination, Antibodies, Monoclonal, 610 Medicine & health, immunization, Disease Models, Animal, Mice, vaccine, Osteoarthritis, Nerve Growth Factor, Pain Management, Animals, Chronic Pain
Abstract

Objectives Nerve growth factor (NGF) has emerged as a key driver of pain in osteoarthritis (OA) and antibodies to NGF are potent analgesics in human disease. Here, we validate a novel vaccine strategy to generate anti-NGF antibodies for reversal of pain behaviour in a surgical model of OA. Methods Virus-like particles were derived from the cucumber mosaic virus (CuMV) and coupled to expressed recombinant NGF to create the vaccine. 10-week-old male mice underwent partial meniscectomy to induce OA or sham-surgery. Spontaneous pain behaviour was measured by Linton incapacitance and OA severity was quantified using OARSI histological scoring. Mice (experimental and a sentinel cohort) were inoculated with CuMVttNGF (Vax) or CuMVttctrl (Mock) either before surgery or once pain was established. Efficacy of anti-NGF from the plasma of sentinel vaccinated mice was measured in vitro using a neurite outgrowth assay in PC12 cells. Results Anti-NGF titres were readily detectable in the vaccinated but not mock vaccinated mice. Regular boosting with fresh vaccine was required to maintain anti-NGF titres as measured in the sentinel cohort. Both prophylactic and therapeutic vaccination demonstrated a reversal of pain behaviour by incapacitance testing, and a meta-analysis of the two studies showing analgesia at peak anti-NGF titres was highly statistically significant. Serum anti-NGF was able to inhibit neurite outgrowth equivalent to around 150 ug/mL of recombinant monoclonal antibody. Conclusions This study demonstrates therapeutic efficacy of a novel NGF vaccine strategy that reversibly alleviates spontaneous pain behaviour in surgically induced murine OA.

Published
2019

11. Overview of approved and upcoming vaccines for SARS-CoV-2: a living review.

Author

Alderson, Jennifer, Batchelor, Vicky, O'Hanlon, Miriam, Cifuentes, Liliana, Richter, Felix Clemens, and Kopycinski, Jakub

Subjects
VACCINE approval, SARS-CoV-2, COVID-19 vaccines, COVID-19
Abstract

The rapid design and implementation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines is testament to a successfully coordinated global research effort. While employing a variety of different technologies, some of which have been used for the first time, all approved vaccines demonstrate high levels of efficacy with excellent safety profiles. Despite this, there remains an urgent global demand for coronavirus disease 2019 vaccines that require further candidates to pass phase 3 clinical trials. In the expectation of SARS-CoV-2 becoming endemic, researchers are looking to adjust the vaccine constructs to tackle emerging variants. In this review, we outline different platforms used for approved vaccines and summarize latest research data with regards to immunogenicity, dosing regimens and efficiency against emerging variants. [ABSTRACT FROM AUTHOR]

Published
2021
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12. 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

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., and Lambe, Teresa

Published
2021
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