Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2

Dami A. Collier, Isabella A. T. M. Ferreira, Prasanti Kotagiri, Rawlings P. Datir, Eleanor Y. Lim, Emma Touizer, Bo Meng, Adam Abdullahi, Anne Elmer, Nathalie Kingston, Barbara Graves, Emma Gresley, Daniela Caputo, Laura Bergamaschi, Kenneth G. C. Smith, John R. Bradley, Lourdes Ceron-Gutierrez, Paulina Cortes-Acevedo, Gabriela Barcenas-Morales, Michelle A. Linterman, Laura E. McCoy, Chris Davis, Emma Thomson, Paul A. Lyons, Eoin McKinney (), Rainer Doffinger (), Mark Wills () and Ravindra K. Gupta ()
Additional contact information
Dami A. Collier: Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID)
Isabella A. T. M. Ferreira: Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID)
Prasanti Kotagiri: Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID)
Rawlings P. Datir: Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID)
Eleanor Y. Lim: University of Cambridge
Emma Touizer: University College London
Bo Meng: Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID)
Adam Abdullahi: Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID)
Anne Elmer: NIHR Bioresource
Nathalie Kingston: NIHR Bioresource
Barbara Graves: NIHR Bioresource
Emma Gresley: NIHR Bioresource
Daniela Caputo: NIHR Bioresource
Laura Bergamaschi: Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID)
Kenneth G. C. Smith: Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID)
John R. Bradley: University of Cambridge
Lourdes Ceron-Gutierrez: Addenbrookes Hospital
Paulina Cortes-Acevedo: Laboratorio de Inmunología, FES-Cuautitlán, UNAM
Gabriela Barcenas-Morales: Laboratorio de Inmunología, FES-Cuautitlán, UNAM
Michelle A. Linterman: Immunology Programme, Babraham Institute
Laura E. McCoy: University College London
Chris Davis: University of Glasgow
Emma Thomson: University of Glasgow
Paul A. Lyons: Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID)
Eoin McKinney: Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID)
Rainer Doffinger: University of Cambridge, Cambridge Biomedical Campus
Mark Wills: Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID)
Ravindra K. Gupta: Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID)

Nature, 2021, vol. 596, issue 7872, 417-422

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 age1. Here we analysed immune responses following vaccination with the BNT162b2 mRNA vaccine2 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.

Date: 2021
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DOI: 10.1038/s41586-021-03739-1

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