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

• DOI: 10.1038/s41586-021-03739-1
• Publication Date: 2021-06-30T16:04:37Z
• Authors: Dami A. Collier; Isabella A. T. M....; Prasanti Kotagiri; Rawlings P. Datir; Eleanor Y. Lim; Emma Touizer; Bo Meng; Adam Abdullahi; ; ; Stephen Baker; Gordon Dougan; Christoph Hess; Nathalie Kingston; Paul J. Lehner; Paul A. Lyons; Nicholas J. Matheson; Willem H. Owehand; Caroline Saunders; Charlotte Summers; James E. D. Thave...; Mark Toshner; Michael P. Weekes; Patrick Maxwell; Ashley Shaw; ; Ashlea Bucke; Jo Calder; Laura Canna; Jason Domingo; Anne Elmer; Stewart Fuller; Julie Harris; Sarah Hewitt; Jane Kennet; Sherly Jose; Jenny Kourampa; Anne Meadows; Criona O’Brien; Jane Price; Cherry Publico; Rebecca Rastall; Carla Ribeiro; Jane Rowlands; Valentina Ruffolo; Hugo Tordesillas; ; Ben Bullman; Benjamin J. Dunmore; Stuart Fawke; Stefan Gräf; Josh Hodgson; Christopher Huang; Kelvin Hunter; Emma Jones; Ekaterina Legchenko; Cecilia Matara; Jennifer Martin; Federica Mescia; Ciara O’Donnell; Linda Pointon; Nicole Pond; Joy Shih; Rachel Sutcliffe; Tobias Tilly; Carmen Treacy; Zhen Tong; Jennifer Wood; Marta Wylot; ; Laura Bergamaschi; Ariana Betancourt; Georgie Bower; Chiara Cossetti; Aloka De Sa; Madeline Epping; Stuart Fawke; Nick Gleadall; Richard Grenfell; Andrew Hinch; Oisin Huhn; Sarah Jackson; Isobel Jarvis; Ben Krishna; Daniel Lewis; Joe Marsden; Francesca Nice; Georgina Okecha; Ommar Omarjee; Marianne Perera; Martin Potts; Nathan Richoz; Veronika Romashova; Natalia Savinykh ...; Rahul Sharma; Luca Stefanucci; Jonathan Stephens; Mateusz Strezlecki; Lori Turner; ; Eckart M. D. D. D...; Katherine Bunclark; Masa Josipovic; Michael Mackay; Alice Michael; Sabrina Rossi; Mayurun Selvan; Sarah Spencer; Cissy Yong; ; Ali Ansaripour; Alice Michael; Lucy Mwaura; Caroline Patterson; Gary Polwarth; ; Petra Polgarova; Giovanni di Stefano; ; Codie Fahey; Rachel Michel; ; Sze-How Bong; Jerome D. Coudert; Elaine Holmes; ; John Allison; Helen Butcher; Daniela Caputo; Debbie Clapham-Riley; Eleanor Dewhurst; Anita Furlong; Barbara Graves; Jennifer Gray; Tasmin Ivers; Mary Kasanicki; Emma Le Gresley; Rachel Linger; Sarah Meloy; Francesca Muldoon; Nigel Ovington; Sofia Papadia; Isabel Phelan; Hannah Stark; Kathleen E. Stirrups; Paul Townsend; Neil Walker; Jennifer Webster; Anne Elmer; Nathalie Kingston; Barbara Graves; Emma Le Gresley; Daniela Caputo; Laura Bergamaschi; Kenneth G. C. Smith; John R. Bradley; Lourdes Ceron-Gut...; Paulina Cortes-Ac...; Gabriela Barcenas...; Michelle A. Linte...; Laura E. McCoy; Chris Davis; Emma Thomson; Paul A. Lyons; Eoin McKinney; Rainer Doffinger; Mark Wills; Ravindra K. Gupta
• Keywords: Adult; Male; 0301 basic medicine; Aging; COVID-19 Vaccines; [SDV]Life Sciences [q-bio]; Health Personnel; T-Lymphocytes; Immunization, Secondary; 610; /13/106; Antibodies, Viral; Article; Antibodies; /38; Interferon-gamma; 03 medical and health sciences; Humans; BNT162 Vaccine; /631/326/596/4130; Adult; Aged; Aged, 80 and over; Aging; Antibodies, Neutralizing; Antibodies, Viral; Autoantibodies; B-Lymphocytes; BNT162 Vaccine; COVID-19 Vaccines; Female; Health Personnel; Humans; Immunization, Secondary; Immunoglobulin A; Immunoglobulin Class Switching; Immunoglobulin G; Immunologic Memory; Inflammation; Interferon-gamma; Interleukin-2; Male; Middle Aged; SARS-CoV-2; Somatic Hypermutation, Immunoglobulin; Spike Glycoprotein, Coronavirus; T-Lymphocytes; Vaccination; Vaccines, Synthetic; Immunity; Aged; Autoantibodies; Aged, 80 and over; Inflammation; Sars-Cov-2; B-Lymphocytes; Vaccines, Synthetic; SARS-CoV-2; Vaccination; Immunity; article; Middle Aged; 16. Peace & justice; Antibodies, Neutralizing; Immunoglobulin Class Switching; Immunoglobulin A; 3. Good health; Immunoglobulin G; Spike Glycoprotein, Coronavirus; Antibodies; Sars-Cov-2; Interleukin-2; Female; /38/39; Somatic Hypermutation, Immunoglobulin; mRNA Vaccines; Immunologic Memory; /631/250/2152/2153/1291

AbstractAlthough 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.