AUTHOR=Byrne Joanne , Gu Lili , Garcia-Leon Alejandro , Gaillard Colette Marie , Saini Gurvin , Alalwan Dana , Tomás-Cortázar Julen , Kenny Grace , Donohue Sean , Reynolds Bearach , O’Gorman Tessa , Landay Alan , Doran Peter , Stemler Jannik , Koehler Philipp , Cox Rebecca Jane , Olesen Ole F. , Lelievre Jean-Daniel , O’Broin Cathal , Savinelli Stefano , Feeney Eoin R. , O’Halloran Jane A. , Cotter Aoife , Horgan Mary , Kelly Christine , Sadlier Corrina , de Barra Eoghan , Cornely Oliver A. , Gautier Virginie , Mallon Patrick WG , All Ireland Infectious Diseases cohort study and VACCELERATE consortium , Cotter A. , Muldoon E. , Sheehan G. , McGinty T. , Lambert J. S. , O’Gorman T. , Kelly C. , Leamy K. , Byrne J. , Kenny G. , McCann K. , McCann R. , O’Broin C. , Savinelli S. , O’Halloran J. , Feeney E. , Mallon P. W. G. , Leon A. Garcia , Miles S. , Alalwan D. , Negi R. , Saini G. , Moore E. , Barra E. de , McConkey S. , Hurley K. , Jacob B. , Lyons F. , Horgan M. , Sadlier C. , Bracken T. , Whelan B. , Low J , Yousif O , McNicholas B. , Courtney G. , O’Maoldomhnaigh C. , Gavin P. , Neuhann Julia M. , Stemler Jannik , Bethe Ullrich , Heringer Sarah , Salmanton-Garcı́a Jon , Tischmann Lea , Cüppers Arnd , Grothe Jan , Koehler Philipp , Cornely Oliver A. , Carcas Antonio J. , Frías-Iniesta Jesús , Akova Murat , Leon Alejandro Garcia , Mallon Patrick , Negi Riya , Gaillard Colette , Saini Gurvin , Lammens Christine , Hotterbeekx An , Loens Katherine , Malhotra-Kumar Surbhi , Goossens Herman , Kumar-Singh Samir , König Franz , Yeghiazaryan Lusine , Posch Martin TITLE=Robust and persistent B-cell responses following SARS-CoV-2 vaccine determine protection from SARS-CoV-2 infection JOURNAL=Frontiers in Immunology VOLUME=15 YEAR=2024 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1445653 DOI=10.3389/fimmu.2024.1445653 ISSN=1664-3224 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.