TY - JOUR
T1 - Robust and persistent B-cell responses following SARS-CoV-2 vaccine determine protection from SARS-CoV-2 infection
AU - Byrne, Joanne
AU - Gu, Lili
AU - Garcia-Leon, Alejandro
AU - Gaillard, Colette Marie
AU - Saini, Gurvin
AU - Alalwan, Dana
AU - Tomás-Cortázar, Julen
AU - Kenny, Grace
AU - Donohue, Sean
AU - Reynolds, Bearach
AU - O’Gorman, Tessa
AU - Landay, Alan
AU - Doran, Peter
AU - Stemler, Jannik
AU - Koehler, Philipp
AU - Cox, Rebecca Jane
AU - Olesen, Ole F.
AU - Lelievre, Jean Daniel
AU - O’Broin, Cathal
AU - Savinelli, Stefano
AU - Feeney, Eoin R.
AU - O’Halloran, Jane A.
AU - Cotter, Aoife
AU - Horgan, Mary
AU - Kelly, Christine
AU - Sadlier, Corrina
AU - de Barra, Eoghan
AU - Cornely, Oliver A.
AU - Gautier, Virginie
AU - Mallon, Patrick W.G.
N1 - Publisher Copyright:
Copyright © 2024 Byrne, Gu, Garcia-Leon, Gaillard, Saini, Alalwan, Tomás-Cortázar, Kenny, Donohue, Reynolds, O’Gorman, Landay, Doran, Stemler, Koehler, Cox, Olesen, Lelievre, O’Broin, Savinelli, Feeney, O’Halloran, Cotter, Horgan, Kelly, Sadlier, de Barra, Cornely, Gautier, Mallon and All Ireland Infectious Diseases cohort study and VACCELERATE consortium.
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
KW - B cells
KW - COVID-19
KW - COVID-19 vaccine
KW - immunogenicity
KW - SARS-CoV-2
KW - T cells
UR - http://www.scopus.com/inward/record.url?scp=85205528356&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85205528356&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2024.1445653
DO - 10.3389/fimmu.2024.1445653
M3 - Article
C2 - 39355249
AN - SCOPUS:85205528356
SN - 1664-3224
VL - 15
JO - Frontiers in immunology
JF - Frontiers in immunology
M1 - 1445653
ER -