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

• Published in: Nature (London) Vol. 596; no. 7872; pp. 417 - 422
• Main Authors: Collier, Dami A., Ferreira, Isabella A. T. M., Kotagiri, Prasanti, Datir, Rawlings P., Lim, Eleanor Y., Touizer, Emma, Meng, Bo, Abdullahi, Adam, Elmer, Anne, Kingston, Nathalie, Graves, Barbara, Le Gresley, Emma, Caputo, Daniela, Bergamaschi, Laura, Smith, Kenneth G. C., Bradley, John R., Ceron-Gutierrez, Lourdes, Cortes-Acevedo, Paulina, Barcenas-Morales, Gabriela, Linterman, Michelle A., McCoy, Laura E., Davis, Chris, Thomson, Emma, Lyons, Paul A., McKinney, Eoin, Doffinger, Rainer, Wills, Mark, Gupta, Ravindra K.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 19.08.2021; Nature Publishing Group
• Subjects: 13/106; 38; 38/39; 631/250/2152/2153/1291; 631/326/596/4130; Adult; Age; Age groups; Aged; Aged, 80 and over; Aging - blood; Aging - immunology; Antibodies; Antibodies, Neutralizing - blood; Antibodies, Neutralizing - immunology; Antibodies, Viral - blood; Antibodies, Viral - immunology; Autoantibodies - immunology; B-Lymphocytes - cytology; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; BNT162 Vaccine; CD4 antigen; Cloning; COVID-19; COVID-19 Vaccines - administration & dosage; COVID-19 Vaccines - immunology; Cytokines; Cytomegalovirus; Demographic aspects; Female; Health aspects; Health Personnel; Heterogeneity; Humanities and Social Sciences; Humans; Immune response; Immune system; Immunity - genetics; Immunization, Secondary; Immunoglobulin A; Immunoglobulin A - immunology; Immunoglobulin Class Switching; Immunoglobulin G; Immunoglobulin G - genetics; Immunoglobulin G - immunology; Immunologic Memory - immunology; Immunological memory; Inflammation - blood; Inflammation - immunology; Interferon; Interferon-gamma - immunology; Interleukin 2; Interleukin-2 - immunology; Lymphocytes; Lymphocytes B; Lymphocytes T; Male; Medical personnel; Memory cells; Middle Aged; mRNA; mRNA Vaccines; multidisciplinary; Neutralization; Older people; Peptides; Physiological aspects; Proteins; SARS-CoV-2 - immunology; Science; Science (multidisciplinary); Severe acute respiratory syndrome coronavirus 2; Somatic hypermutation; Somatic Hypermutation, Immunoglobulin; Spike Glycoprotein, Coronavirus - immunology; T-Lymphocytes - immunology; Vaccination; Vaccine efficacy; Vaccines; Vaccines, Synthetic - administration & dosage; Vaccines, Synthetic - immunology; United States
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/s41586-021-03739-1

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. Individuals over eighty years of age are less likely to mount a good immune response against SARS-CoV-2 (measured by neutralization titres) after the first dose of the BNT162b2 mRNA vaccine, but achieve good neutralization after the second dose.