1. T cell and antibody responses induced by a single dose of ChAdOx1 nCoV-19 (AZD1222) vaccine in a phase 1/2 clinical trial
- Author
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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.
- Published
- 2020
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