Frontiers in Immunology (Sep 2024)

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

  • Joanne Byrne,
  • Joanne Byrne,
  • Lili Gu,
  • Alejandro Garcia-Leon,
  • Colette Marie Gaillard,
  • Gurvin Saini,
  • Dana Alalwan,
  • Julen Tomás-Cortázar,
  • Grace Kenny,
  • Grace Kenny,
  • Sean Donohue,
  • Bearach Reynolds,
  • Tessa O’Gorman,
  • Tessa O’Gorman,
  • Alan Landay,
  • Peter Doran,
  • Jannik Stemler,
  • Jannik Stemler,
  • Philipp Koehler,
  • Philipp Koehler,
  • Rebecca Jane Cox,
  • Ole F. Olesen,
  • Jean-Daniel Lelievre,
  • Cathal O’Broin,
  • Cathal O’Broin,
  • Stefano Savinelli,
  • Stefano Savinelli,
  • Eoin R. Feeney,
  • Eoin R. Feeney,
  • Jane A. O’Halloran,
  • Jane A. O’Halloran,
  • Aoife Cotter,
  • Aoife Cotter,
  • Mary Horgan,
  • Mary Horgan,
  • Christine Kelly,
  • Christine Kelly,
  • Corrina Sadlier,
  • Eoghan de Barra,
  • Eoghan de Barra,
  • Oliver A. Cornely,
  • Oliver A. Cornely,
  • Oliver A. Cornely,
  • Virginie Gautier,
  • Patrick WG Mallon,
  • Patrick WG Mallon,
  • All Ireland Infectious Diseases cohort study and VACCELERATE consortium,
  • A. Cotter,
  • E. Muldoon,
  • G. Sheehan,
  • T. McGinty,
  • J. S. Lambert,
  • T. O’Gorman,
  • C. Kelly,
  • K. Leamy,
  • J. Byrne,
  • G. Kenny,
  • K. McCann,
  • R. McCann,
  • C. O’Broin,
  • S. Savinelli,
  • J. O’Halloran,
  • E. Feeney,
  • P. W. G. Mallon,
  • A. Garcia Leon,
  • S. Miles,
  • D. Alalwan,
  • R. Negi,
  • G. Saini,
  • E. Moore,
  • E. de Barra,
  • S. McConkey,
  • K. Hurley,
  • B. Jacob,
  • F. Lyons,
  • M. Horgan,
  • C. Sadlier,
  • T. Bracken,
  • B. Whelan,
  • J Low,
  • O Yousif,
  • B. McNicholas,
  • G. Courtney,
  • C. O’Maoldomhnaigh,
  • P. Gavin,
  • Julia M. Neuhann,
  • Jannik Stemler,
  • Ullrich Bethe,
  • Sarah Heringer,
  • Jon Salmanton-Garcı́a,
  • Lea Tischmann,
  • Arnd Cüppers,
  • Jan Grothe,
  • Philipp Koehler,
  • Oliver A. Cornely,
  • Antonio J. Carcas,
  • Jesús Frías-Iniesta,
  • Murat Akova,
  • Alejandro Garcia Leon,
  • Patrick Mallon,
  • Riya Negi,
  • Colette Gaillard,
  • Gurvin Saini,
  • Christine Lammens,
  • An Hotterbeekx,
  • Katherine Loens,
  • Surbhi Malhotra-Kumar,
  • Herman Goossens,
  • Samir Kumar-Singh,
  • Franz König,
  • Lusine Yeghiazaryan,
  • Martin Posch

DOI
https://doi.org/10.3389/fimmu.2024.1445653
Journal volume & issue
Vol. 15

Abstract

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IntroductionA 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.MethodsAdults 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.ResultsOf 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).DiscussionRobust 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.

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