Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2
Authors: Collier Dami A. , Ferreira Isabella A. T. M. , Kotagiri Prasanti , Datir Rawlings P. , Lim Eleanor Y. , Touizer Emma , Meng Bo , Abdullahi Adam ,   The CITIID-NIHR BioResource COVID-19 Collaboration,   Principal Investigators, Baker Stephen , Dougan Gordon , Hess Christoph , Kingston Nathalie , Lehner Paul J. , Lyons Paul A. , Matheson Nicholas J. , Owehand Willem H. , Saunders Caroline , Summers Charlotte , Thaventhiran James E. D. , Toshner Mark , Weekes Michael P. , Maxwell Patrick , Shaw Ashley ,   CRF and Volunteer Research Nurses, Bucke Ashlea , Calder Jo , Canna Laura , Domingo Jason , Elmer Anne , Fuller Stewart , Harris Julie , Hewitt Sarah , Kennet Jane , Jose Sherly , Kourampa Jenny , Meadows Anne , O’Brien Criona , Price Jane , Publico Cherry , Rastall Rebecca , Ribeiro Carla , Rowlands Jane , Ruffolo Valentina , Tordesillas Hugo ,   Sample Logistics, Bullman Ben , Dunmore Benjamin J. , Fawke Stuart , Gräf Stefan , Hodgson Josh , Huang Christopher , Hunter Kelvin , Jones Emma , Legchenko Ekaterina , Matara Cecilia , Martin Jennifer , Mescia Federica , O’Donnell Ciara , Pointon Linda , Pond Nicole , Shih Joy , Sutcliffe Rachel , Tilly Tobias , Treacy Carmen , Tong Zhen , Wood Jennifer , Wylot Marta ,   Sample Processing and Data Acquisition, Bergamaschi Laura , Betancourt Ariana , Bower Georgie , Cossetti Chiara , De Sa Aloka , Epping Madeline , Fawke Stuart , Gleadall Nick , Grenfell Richard , Hinch Andrew , Huhn Oisin , Jackson Sarah , Jarvis Isobel , Krishna Ben , Lewis Daniel , Marsden Joe , Nice Francesca , Okecha Georgina , Omarjee Ommar , Perera Marianne , Potts Martin , Richoz Nathan , Romashova Veronika , Yarkoni Natalia Savinykh , Sharma Rahul , Stefanucci Luca , Stephens Jonathan , Strezlecki Mateusz , Turner Lori ,   Clinical Data Collection, D. D. De Bie Eckart M. , Bunclark Katherine , Josipovic Masa , Mackay Michael , Michael Alice , Rossi Sabrina , Selvan Mayurun , Spencer Sarah , Yong Cissy ,   Royal Papworth Hospital ICU, Ansaripour Ali , Michael Alice , Mwaura Lucy , Patterson Caroline , Polwarth Gary ,   Addenbrooke’s Hospital ICU, Polgarova Petra , di Stefano Giovanni ,   Cambridge and Peterborough Foundation Trust, Fahey Codie , Michel Rachel ,   ANPC and Centre for Molecular Medicine and Innovative Therapeutics, Bong Sze-How , Coudert Jerome D. , Holmes Elaine ,   NIHR BioResource4, Allison John , Butcher Helen , Caputo Daniela , Clapham-Riley Debbie , Dewhurst Eleanor , Furlong Anita , Graves Barbara , Gray Jennifer , Ivers Tasmin , Kasanicki Mary , Le Gresley Emma , Linger Rachel , Meloy Sarah , Muldoon Francesca , Ovington Nigel , Papadia Sofia , Phelan Isabel , Stark Hannah , Stirrups Kathleen E. , Townsend Paul , Walker Neil , Webster Jennifer , 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. 
Published: June 2021

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.