Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2
Dami A. Collier(University of Cambridge), Isabella A.T.M. Ferreira(University of Cambridge), Prasanti Kotagiri(University of Cambridge), Rawlings Datir(University of Cambridge), Eleanor Y. Lim(University of Cambridge), Emma Touizer(University College London), Bo Meng(University of Cambridge), Adam Abdullahi, Principal Investigators(University of Cambridge), Stephen Baker(University of Cambridge), Gordon Dougan(University of Cambridge), Christoph Hess(University of Cambridge), Nathalie Kingston(University of Cambridge), Paul J. Lehner(University of Cambridge), Paul A. Lyons(University of Cambridge), Nicholas J. Matheson(University of Cambridge), Willem H. Owehand(University of Cambridge), Caroline Saunders(Cambridge University Hospitals NHS Foundation Trust), Charlotte Summers(University of Cambridge), James Thaventhiran(University of Cambridge), Mark Toshner(University of Cambridge), Michael P. Weekes(University of Cambridge), Patrick H. Maxwell(University of Cambridge), Ashley Shaw(Cambridge University Hospitals NHS Foundation Trust), Ashlea Bucke(Cambridge University Hospitals NHS Foundation Trust), Jo Calder(Cambridge University Hospitals NHS Foundation Trust), Laura Canna(Cambridge University Hospitals NHS Foundation Trust), Jason Domingo(Cambridge University Hospitals NHS Foundation Trust), Anne Elmer(University of Cambridge), Stewart Fuller(Cambridge University Hospitals NHS Foundation Trust), Julie Harris(University of Cambridge), Sarah Hewitt(Cambridge University Hospitals NHS Foundation Trust), Jane Kennet(Cambridge University Hospitals NHS Foundation Trust), Sherly Jose(Cambridge University Hospitals NHS Foundation Trust), Jenny Kourampa(Cambridge University Hospitals NHS Foundation Trust), Anne Meadows(Cambridge University Hospitals NHS Foundation Trust), Criona O’Brien(Cambridge University Hospitals NHS Foundation Trust), Jane Price(Cambridge University Hospitals NHS Foundation Trust), Cherry Publico(Cambridge University Hospitals NHS Foundation Trust), Rebecca Rastall(Cambridge University Hospitals NHS Foundation Trust), Carla M. S. Ribeiro(Cambridge University Hospitals NHS Foundation Trust), Jane Rowlands(Cambridge University Hospitals NHS Foundation Trust), Valentina Ruffolo(University of Cambridge), Hugo Tordesillas(Cambridge University Hospitals NHS Foundation Trust), Sample Logistics(University of Cambridge), Ben Bullman(University of Cambridge), Benjamin J. Dunmore(University College London), Stuart Fawke(University of Cambridge), Stefan Ting Graf(University of Cambridge), Josh Hodgson(University College London), Christopher Huang(University College London), Kelvin Hunter(University of Cambridge), Emma Jones(University of Cambridge), Ekaterina Legchenko(University College London), Cecilia Matara(University College London), Jennifer Martin(University of Cambridge), Federica Mescia(University of Cambridge), Ciara O’Donnell(University College London), Linda Pointon(University College London), Nicole Pond(University of Cambridge), Joy Shih(University College London), Rachel Sutcliffe(University College London), Tobias Tilly(University of Cambridge), Carmen Treacy(University of Cambridge), Zhen Tong(University of Cambridge), Jennifer Wood(University of Cambridge), Marta Wylot(University of Cambridge), Sample Processing and Data Acquisition(University of Cambridge), Laura Bergamaschi(University of Cambridge), Ariana Betancourt(University of Cambridge), Georgie Bower(University of Cambridge), Chiara Cossetti(University of Cambridge), Aloka De(Rosie Hospital), Madeline Epping(University of Cambridge), Stuart Fawke(University of Cambridge), Nick Gleadall(University of Cambridge), Richard Grenfell(University of Cambridge), Andrew Hinch(University of Cambridge), Oisín Huhn(Rosie Hospital), Sarah Jackson(University College London), Isobel Jarvis(University College London), Benjamin A. Krishna(University College London), D. J. Lewis(University College London), Joe Marsden(University College London), Francesca Nice(University of Cambridge), Georgina Okecha(University College London), Ommar Omarjee(University College London), Marianne Perera(University of Cambridge), Martin Potts(University of Cambridge), Nathan Richoz(University of Cambridge), Veronika Romashova(University of Cambridge), Natalia Savinykh Yarkoni(University College London), Rahul Sharma(University College London), Luca Stefanucci(University of Cambridge), Jonathan Stephens(University of Cambridge), Mateusz Strezlecki(University of Cambridge), Lori Turner(University of Cambridge), Eckart M. D. D. De Bie(Hycult Biotech (Netherlands)), Katherine Bunclark(Addenbrooke's Hospital), Maša Josipović(Papworth Hospital NHS Foundation Trust), Michael Mackay(Papworth Hospital NHS Foundation Trust), Alice Michael(Papworth Hospital NHS Foundation Trust), Sabrina Rossi(Papworth Hospital NHS Foundation Trust), Mayurun Selvan(Papworth Hospital NHS Foundation Trust), Sarah Spencer(Hycult Biotech (Netherlands)), Cissy Yong(Addenbrooke's Hospital), Ali Ansaripour(Fulbourn Hospital), Alice Michael(Fulbourn Hospital), Lucy Mwaura(Murdoch University), Caroline Patterson(Murdoch University), Gary Polwarth(Murdoch University), Petra Polgarova(University of Cambridge), Giovanni Di Stefano(University of Cambridge), Codie Fahey(University of Cambridge), Rachel Michel(University of Cambridge), Sze-How Bong(Murdoch University), Jérôme D. Coudert(Murdoch University), Elaine Holmes(Murdoch University), NIHR BioResource4(University of Cambridge), John Allison(University of Cambridge), Helen Butcher(University of Cambridge), Daniela Caputo(University of Cambridge), Debbie Clapham-Riley(University of Cambridge), Eleanor Dewhurst(University of Cambridge), Anita Furlong(University of Cambridge), Barbara Graves(University of Cambridge), Jennifer Gray(University of Cambridge), Tasmin Ivers(University of Cambridge), Mary Kasanicki(University of Cambridge), Emma Le Gresley(University of Cambridge), Rachel Linger(University of Cambridge), Sarah Meloy(University of Cambridge), Francesca Muldoon(University of Cambridge), Nigel Ovington(University of Cambridge), Sofia Papadia(University of Cambridge), Isabel Phelan(University of Cambridge), Hannah Stark(University of Cambridge), Kathleen Stirrups(University of Cambridge), Paul Townsend(Addenbrooke's Hospital), Neil Walker(Universidad de Cuautitlán Izcalli), Jennifer Webster(University of Cambridge), Anne Elmer(Babraham Institute), Nathalie Kingston(University of Cambridge), Barbara Graves(MRC University of Glasgow Centre for Virus Research), Emma Le Gresley(University of Cambridge), Daniela Caputo(University of Cambridge), Laura Bergamaschi(University of Cambridge), Kenneth G. C. Smith(University of Cambridge), John R. Bradley(University of Cambridge), Lourdes Ceron‐Gutierrez(University of Cambridge), Paulina Cortes-Acevedo(Universidad de Cuautitlán Izcalli), Gabriela Barcenas‐Morales(Universidad de Cuautitlán Izcalli), Michelle A. Linterman(Babraham Institute), Laura E. McCoy(University College London), Christopher Davis(MRC University of Glasgow Centre for Virus Research), Emma C. Thomson(MRC University of Glasgow Centre for Virus Research), Paul A. Lyons(University of Cambridge), Eoin McKinney(University of Cambridge), Rainer Döffinger(University of Cambridge), Mark R. Wills(University of Cambridge), Ravindra K. Gupta(University of Cambridge)
Cited by 815Open Access
Abstract
Abstract Although two-dose mRNA vaccination provides excellent protection against SARS-CoV-2, there is little information about vaccine efficacy against variants of concern (VOC) in individuals above eighty years of age 1 . Here we analysed immune responses following vaccination with the BNT162b2 mRNA vaccine 2 in elderly participants and younger healthcare workers. Serum neutralization and levels of binding IgG or IgA after the first vaccine dose were lower in older individuals, with a marked drop in participants over eighty years old. Sera from participants above eighty showed lower neutralization potency against the B.1.1.7 (Alpha), B.1.351 (Beta) and P.1. (Gamma) VOC than against the wild-type virus and were more likely to lack any neutralization against VOC following the first dose. However, following the second dose, neutralization against VOC was detectable regardless of age. The frequency of SARS-CoV-2 spike-specific memory B cells was higher in elderly responders (whose serum showed neutralization activity) than in non-responders after the first dose. Elderly participants showed a clear reduction in somatic hypermutation of class-switched cells. The production of interferon-γ and interleukin-2 by SARS-CoV-2 spike-specific T cells was lower in older participants, and both cytokines were secreted primarily by CD4 T cells. We conclude that the elderly are a high-risk population and that specific measures to boost vaccine responses in this population are warranted, particularly where variants of concern are circulating.
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