Journal Article

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

Koehler, Philipp, O’Broin, Cathal, Lelievre, Jean-Daniel, Stemler, Jannik, Sadlier, Corrina, Garcia-Leon, Alejandro, Gaillard, Colette Marie, Alalwan, Dana, de Barra, Eoghan, Cox, Rebecca Jane, Tomás-Cortázar, Julen, Reynolds, Bearach, Olesen, Ole F., Saini, Gurvin, Cornely, Oliver A., Gautier, Virginie, Horgan, Mary, Donohue, Sean, Landay, Alan, Doran, Peter, O’Halloran, Jane A., Kelly, Christine, Feeney, Eoin R., Kenny, Grace, Gu, Lili, Savinelli, Stefano, Cotter, Aoife, O’Gorman, Tessa, Mallon, Patrick WG, Byrne, Joanne

2024

Overview

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. 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. 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). 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.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Adult / Aged / Antibodies / Antibodies, Viral - blood / Antibodies, Viral - immunology / Antigens / B cells / B-Lymphocytes - immunology / Cells / Cohort analysis / Comparative analysis / Coronaviruses / COVID-19 / COVID-19 - immunology / COVID-19 - prevention & control / COVID-19 vaccine / COVID-19 vaccines / COVID-19 Vaccines - immunology / Enzyme-linked immunosorbent assay / Female / Humans / Immune response / Immunity (Disease) / immunogenicity / Immunologic Memory / Immunological memory / Immunology / Infections / Infectious diseases / Leukocytes (mononuclear) / Lymphatic system / Lymphocytes / Lymphocytes B / Lymphocytes T / Male / Memory B Cells - immunology / Memory cells / Middle Aged / Pathogens / Peptides / Peripheral blood mononuclear cells / Plasma / Prospective Studies / SARS-CoV-2 / SARS-CoV-2 - immunology / Severe acute respiratory syndrome coronavirus 2 / Spike Glycoprotein, Coronavirus - immunology / Statistical analysis / Survival analysis / T cells / T-Lymphocytes - immunology / Vaccines