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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Vaccines and Molecular Therapeutics
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1538453
This article is part of the Research Topic SARS-CoV-2 Vaccines Beyond the Pandemic Era View all 22 articles

Enhanced T-cell immunity and lower humoral responses following 5-dose SARS-CoV-2 vaccination in patients with inborn errors of immunity compared with healthy controls

Provisionally accepted
Vitor Gabriel Lopes da Silva Vitor Gabriel Lopes da Silva 1*Gabriela Justamante Händel Schmitz Gabriela Justamante Händel Schmitz 2Kathleen E Sullivan Kathleen E Sullivan 3,4Júlia Barbate Pintão Júlia Barbate Pintão 1Maria Izabel de Haro Azinar Maria Izabel de Haro Azinar 1Carolina Sanchez Aranda Carolina Sanchez Aranda 1Maria Isabel de Moraes-Pinto Maria Isabel de Moraes-Pinto 1*
  • 1 Federal University of São Paulo, São Paulo, Brazil
  • 2 University of São Paulo, São Paulo, Rio Grande do Sul, Brazil
  • 3 University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • 4 Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States

The final, formatted version of the article will be published soon.

    Patients with Inborn Errors of Immunity (IEI) are at higher risk of severe SARS-CoV-2 infection. We evaluated humoral and cellular responses to COVID-19 vaccines in Brazilian patients with IEI and healthy controls. Fifty-five patients with IEI (13-61 years) and 60 controls (13-71 years) received inactivated SARS-CoV-2 (CoronaVac), non-replicating virus-vectored (ChAdOx1 nCoV-19, AstraZeneca) or monovalent mRNA (Original strain of BNT162b2, Pfizer-BioNTech) and bivalent mRNA (Original/Omicron BA.1, Pfizer-BioNTech) vaccines and were sampled five times. Diagnoses included common variable immunodeficiency (n=25), specific antibody deficiency (n=9), ataxia-telangiectasia (n=5), X-linked agammaglobulinemia (n=4), PIK3CD-related disorders (n=4), hyper-IgM syndrome (n=4), combined immunodeficiency (n=3), and STAT1 gain-of-function (n=1). Humoral immunity was assessed via multiplex microarray for Spike, Nucleocapsid, RBD-Wuhan, RBD-Delta, RBD-BA1, RBD-BA2 and RBD-BA5 neutralizing antibodies. T-cell responses to Spike and Nucleocapsid were assessed using ELISpot. Patients with IEI exhibited significantly lower levels of Nucleocapsid and RBD-neutralizing antibodies (p < 0.05). Notable differences in RBD-BA.2 (p = 0.008) and IgG-Nucleocapsid (p = 0.010) levels emerged over time. T-cell responses to Spike were stronger in patients with IEI post-booster (405 vs. 149 spot-forming cells/million PBMC; p = 0.002). Both groups showed enhanced Nucleocapsid-specific cellular responses over time (p = 0.017). COVID-19 hospitalization rates among patients with IEI with SARS-CoV-2 diagnosis dropped from 33.3% to zero after the first booster dose. While humoral responses to SARS-CoV-2 vaccines were weaker in patients with IEI, their cellular immunity was similar to controls. Boosters enhanced both humoral and cellular responses. After completion of the vaccination protocol, none of the patients with IEI were hospitalized with COVID-19. Robust T-cell responses may play a critical role in protecting patients with IEI from severe COVID-19 and mortality.

    Keywords: COVID-19 vaccines, Booster, inborn errors of immunity, Primary immunodeficiency disorders, SARS-CoV-2, Microarray, immune response, ELISPOT Enzyme-Linked ImmunoSpot

    Received: 02 Dec 2024; Accepted: 06 Feb 2025.

    Copyright: © 2025 Lopes da Silva, Schmitz, Sullivan, Barbate Pintão, de Haro Azinar, Aranda and de Moraes-Pinto. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Vitor Gabriel Lopes da Silva, Federal University of São Paulo, São Paulo, Brazil
    Maria Isabel de Moraes-Pinto, Federal University of São Paulo, São Paulo, Brazil

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.