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Front Immunol . Robust and persistent B-cell responses following SARS-CoV-2 vaccine determine protection from SARS-CoV-2 infection

tetano

Editor, Senior Moderator
Front Immunol


. 2024 Sep 17:15:1445653.
doi: 10.3389/fimmu.2024.1445653. eCollection 2024. Robust and persistent B-cell responses following SARS-CoV-2 vaccine determine protection from SARS-CoV-2 infection

Joanne Byrne[SUP] 1 2 [/SUP], Lili Gu[SUP] 1 [/SUP], Alejandro Garcia-Leon[SUP] 1 [/SUP], Colette Marie Gaillard[SUP] 1 [/SUP], Gurvin Saini[SUP] 1 [/SUP], Dana Alalwan[SUP] 1 [/SUP], Julen Tomás-Cortázar[SUP] 1 [/SUP], Grace Kenny[SUP] 1 2 [/SUP], Sean Donohue[SUP] 2 [/SUP], Bearach Reynolds[SUP] 2 [/SUP], Tessa O'Gorman[SUP] 1 3 [/SUP], Alan Landay[SUP] 4 [/SUP], Peter Doran[SUP] 5 [/SUP], Jannik Stemler[SUP] 6 7 [/SUP], Philipp Koehler[SUP] 6 7 [/SUP], Rebecca Jane Cox[SUP] 8 [/SUP], Ole F Olesen[SUP] 9 [/SUP], Jean-Daniel Lelievre[SUP] 10 [/SUP], Cathal O'Broin[SUP] 1 2 [/SUP], Stefano Savinelli[SUP] 1 2 [/SUP], Eoin R Feeney[SUP] 1 2 [/SUP], Jane A O'Halloran[SUP] 1 2 [/SUP], Aoife Cotter[SUP] 1 5 [/SUP], Mary Horgan[SUP] 3 5 [/SUP], Christine Kelly[SUP] 1 5 [/SUP], Corrina Sadlier[SUP] 11 [/SUP], Eoghan de Barra[SUP] 12 13 [/SUP], Oliver A Cornely[SUP] 6 7 14 [/SUP], Virginie Gautier[SUP] 1 [/SUP], Patrick Wg Mallon[SUP] 1 2 [/SUP]



Affiliations
Abstract

Introduction: A clear immune correlate of protection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has not been defined. We explored antibody, B-cell, and T-cell responses to the third-dose vaccine and relationship to incident SARS-CoV-2 infection.
Methods: Adults in a prospective cohort provided blood samples at day 0, day 14, and 10 months after the third-dose SARS-CoV-2 vaccine. Participants self-reported incident SARS-CoV-2 infection. Plasma anti-SARS-CoV-2 receptor-binding domain (RBD) and spike-subunit-1 and spike-subunit-2 antibodies were measured. A sub-study assessed SARS-CoV-2-specific plasma and memory B-cell and memory T-cell responses in peripheral blood mononuclear cells by enzyme-linked immunospot. Comparative analysis between participants who developed incident infection and uninfected participants utilised non-parametric t-tests, Kaplan-Meier survival analysis, and Cox proportional hazard ratios.
Results: Of the 132 participants, 47 (36%) reported incident SARS-CoV-2 infection at a median 16.5 (16.25-21) weeks after the third-dose vaccination. RBD titres and B-cell responses, but not T-cell responses, increased after the third-dose vaccine. Whereas no significant difference in day 14 antibody titres or T-cell responses was observed between participants with and without incident SARS-CoV-2 infection, RBD memory B-cell frequencies were significantly higher in those who did not develop infection [10.0% (4.5%-16.0%) versus 4.9% (1.6%-9.3%), p = 0.01]. RBD titres and memory B-cell frequencies remained significantly higher at 10 months than day 0 levels (p < 0.01).
Discussion: Robust antibody and B-cell responses persisted at 10 months following the third-dose vaccination. Higher memory B-cell frequencies, rather than antibody titres or T-cell responses, predicted protection from subsequent infection, identifying memory B cells as a correlate of protection.

Keywords: B cells; COVID-19; COVID-19 vaccine; SARS-CoV-2; T cells; immunogenicity.

 
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