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

Authors :
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
Stafford, Elizabeth
Source :
Nature Medicine
Publication Year :
2020
Publisher :
Springer Science and Business Media LLC, 2020.

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.

Details

Language :
English
ISSN :
1546170X and 10788956
Database :
OpenAIRE
Journal :
Nature Medicine
Accession number :
edsair.doi.dedup.....f382e686a73125c196c2e5527fbe356b
Full Text :
https://doi.org/10.1038/s41591-020-01194-5