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

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

Joanne Byrne et al. Front Immunol. .

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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Conflict of interest statement

JS has received research support by the German Ministry of Education and Research BMBF, Basilea Pharmaceuticals, Noscendo; has received speaker honoraria by AbbVie, Gilead, Hikma and Pfizer; has been a consultant to Gilead, Alvea Vax. and Micron Research PK reports grants or contracts from German Federal Ministry of Research and Education BMBF B-FAST Bundesweites Forschungsnetz Angewandte Surveillance und Testung and NAPKON Nationales Pandemie Kohorten Netz, German National Pandemic Cohort Network of the Network University Medicine NUM and the State of North Rhine-Westphalia; Consulting fees Ambu GmbH, Gilead Sciences, infill healthcare communication GmbH, Mundipharma Resarch Limited, Noxxon N.V. and Pfizer Pharma; Honoraria for lectures from Akademie für Infektionsmedizin e.V., Ambu GmbH, Astellas Pharma, BioRad Laboratories Inc., Datamed GmbH, European Confederation of Medical Mycology, Gilead Sciences, GPR Academy Ruesselsheim, HELIOS Kliniken GmbH, Jazz Pharmaceuticals Germany GmbH, Lahn-Dill-Kliniken GmbH, medupdate GmbH, MedMedia GmbH, MSD Sharp & Dohme GmbH, Pfizer Pharma GmbH, Scilink Comunicación Científica SC, streamedup! GmbH, University Hospital and LMU Munich and VITIS GmbH; Participation on an Advisory Board from Ambu GmbH, Gilead Sciences, Mundipharma Resarch Limited and Pfizer Pharma; A filed patent at the German Patent and Trade Mark Office DE 10 2021 113 007.7; Other non-financial interests from Elsevier, Wiley and Taylor & Francis online outside the submitted work. SS has received financial support by Gilead Sciences, ViiV Healthcare, and MSD for attendance to international conferences. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flow diagram of study population.
Figure 2
Figure 2
SARS-CoV-2–specific antibody titres and relationship with incident infection. (A) Significantly higher SARS-CoV-2–specific anti-RBD, anti-S1, and anti-S2 titres at day 14. *p ≤ 0.0001 compared to pre-vaccine response by Wilcoxon signed-rank test. (B) There was no significant difference in anti-RBD IgG, anti–spike-subunit-1 IgG, or anti–spike-subunit-2 IgG titres at day 14 in those who developed infection and those who did not develop infection. Bars represent median and interquartile range. P-values calculated by Mann–Whitney U test are shown above each comparison. D0, day 0; D14, day 14; RBD, receptor-binding domain; S, spike; S1, spike subunit 1; S2, spike subunit 2; BAU, binding antibody unit; IgG Immunoglobulin G.
Figure 3
Figure 3
SARs-CoV-2–specific B-cell responses and relationship with incident infection. (A) Significantly higher SARS-CoV-2–specific memory B-cell and plasma cell responses at day 14. *p ≤ 0.0001 compared to pre-vaccine response by Wilcoxon signed-rank test. (B) SARS-CoV-2–specific RBD and S plasma cell and memory B-cell responses before the third-dose SARS-CoV-2 vaccination and relationship with incident SARS-CoV-2 infection. Bars represent median and interquartile range. P-value calculated by Mann–Whitney U test are shown above each comparison. (C) SARS-CoV-2–specific RBD and S plasma cell and memory B-cell responses 14 days after the third-dose SARS-CoV-2 vaccination and relationship with incident SARS-CoV-2 infection. D0, day 0; D14, day 14; PBMCs, peripheral blood mononuclear cells; RBD, receptor-binding domain; S, spike; ns, not significant; SFU, spot-forming unit.
Figure 4
Figure 4
SARS-CoV-2–specific memory T-cell responses and relationship with incident infection. (A) There was no significant difference in SARS-CoV-2–specific memory T-cell responses at day 14. P-values calculated by Wilcoxon signed-rank test compared to pre-vaccine responses. (B) There was no significant differences in the day 14 memory T-cell responses between those who developed infection and those who did not develop infection. P-values calculated by Mann–Whitney U test. Bars represent median and interquartile range. S, spike; N, nucleocapsid; SFU, spot-forming unit; PBMCs, peripheral blood mononuclear cells; ns, not significant.
Figure 5
Figure 5
Immune responses at 10 months after the third-dose vaccine. (A) Significantly higher SARS-CoV-2–specific memory B-cell frequencies at 10 months after third-dose vaccine in comparison to day 0 frequencies. (B) Significantly higher anti-RBD, anti-S1, and anti-S2 titres at 10 months after the third-dose vaccine in comparison to day 0 responses. (C) There was no significant difference in SARS-CoV-2–specific memory T-cell responses at month 10 in comparison to day 0 responses. P-value calculated by Wilcoxon signed-rank of responses at 10 months in comparison to day 0 responses. **p = 0.01, *p ≤ 0.0001; ns, not significant. RBD, receptor-binding domain; S, full spike; S1, spike subunit 1; S2, spike subunit 2; N, nucleocapsid; WT, wild type; MBC, memory B cell; PBMCs, peripheral blood mononuclear cells, BAU, binding antibody unit; SFU, spot-forming unit.
Figure 6
Figure 6
Higher SARS-CoV-2–specific memory B-cell frequencies determine survival from SARS-CoV-2 infection. (A) Kaplan–Meier survival curve based on the median SARS-CoV-2 full spike–specific memory B-cell frequencies (33.62% total IgG-secreting B cells) at day 14 after the third-dose SARS-CoV-2 vaccination and incident infection. (B) Kaplan–Meier survival curve based on the median SARS-CoV-2 RBD memory B-cell frequencies (0.95% total IgG-secreting B cells) at day 0 after SARS-CoV-2 vaccination and incident infection. Survival analysis p-value calculated by log-rank (Mantel–Cox) test.
Figure 7
Figure 7
Higher spike-specific memory B-cell frequencies determine survival from SARS-CoV-2 infection at 10 months. Day 14 full spike–specific memory B-cell responses above the median (36.80% total IgG-secreting B cells) were significantly associated with protection from infection in a survival analysis at 10 months after the third-dose vaccination. Survival analysis p-value calculated by log-rank (Mantel–Cox) test.
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References

    1. Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, et al. . Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med. (2020) 383:2603–15. doi: 10.1056/NEJMoa2034577 - DOI - PMC - PubMed
    1. Wang Z, Schmidt F, Weisblum Y, Muecksch F, Barnes CO, Finkin S, et al. . mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants. Nature. (2021) 592:616–22. doi: 10.1038/s41586-021-03324-6 - DOI - PMC - PubMed
    1. Liu Y, Zeng Q, Deng C, Li M, Li L, Liu D, et al. . Robust induction of B cell and T cell responses by a third dose of inactivated SARS-CoV-2 vaccine. Cell Discovery. (2022) 8:10. doi: 10.1038/s41421-022-00373-7 - DOI - PMC - PubMed
    1. Turner JS, O'Halloran JA, Kalaidina E, Kim W, Schmitz AJ, Zhou JQ, et al. . SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses. Nature. (2021) 596:109–13. doi: 10.1038/s41586-021-03738-2 - DOI - PMC - PubMed
    1. Doherty J, O'Morain N, Stack R, Tosetto M, Inzitiari R, O'Reilly S, et al. . Reduced serological response to COVID-19 booster vaccine is associated with reduced B cell memory in patients with inflammatory bowel disease; VARIATION [VAriability in response in IBD againsT SARS-COV-2 immunisatiON. J Crohns Colitis. (2023) 17:1445–56. doi: 10.1093/ecco-jcc/jjad065 - DOI - PubMed

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