ORIGINAL RESEARCH article
Front. Immunol.
Sec. Primary Immunodeficiencies
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1659259
Impact of CMV latency on T-cell responses to COVID-19 vaccination among predominantly antibody deficient patients
Provisionally accepted
Trinidad Alba-Cano1Roberto Alonso2Héctor Balastegui1
Luz Yadira Bravo-Gallego3
Paloma Sánchez-Mateos1Mónica Martín-López1
Juana Gil-Herrera1*- 1Division of Immunology. Hospital General Universitario "Gregorio Marañón", Madrid, Spain
- 2Division of Microbiology. Hospital General Universitario Gregorio Marañón, , Spain., Madrid, Spain
- 3Division of Immunology. Hospital Universitario La Paz, Madrid, Spain
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Background: The immunogenicity of mRNA COVID-19 vaccines has been reported as highly variable in patients with inborn errors of immunity (IEI). Objective: To study memory CD4+ T-cell-mediated responses against Spike (S) protein of SARS-CoV-2 along with CMV peptides in a large IEI group composed of mostly predominantly antibody deficient (PAD) patients. Patients and methods: In vitro antigen-specific T-cell anti-S and -CMV responses after two doses of mRNA COVID-19 vaccines were assessed in peripheral blood from 114 IEI patients and 38 healthcare healthy controls (HCHC). Stimulation index (SI) based on the percentages of CD4+ T lymphocytes with effector memory phenotype CD45RA-CD27- (TEM) was quantified by flow cytometry. Results: The IEI patients overall, as well as the two main groups of PAD (i.e. common variable immunodeficiency (CVID) and isotype or functional antibody deficiencies (IOFD)), showed frequencies of responder individuals and median SI against SARS-CoV-2 comparable to HCHC. However, those IEI and CVID subgroups positive for anti-CMV T-cell immunity showed a significantly reduced response (SI) against S-peptides when compared to their IEI and CVID counterparts who were anti-CMV TEM negative. This effect of CMV stratification is independent of age in our patient group. Conclusion: CMV latency negatively impacted CD4+ TEM populations functionality regarding COVID-19 vaccination in CVID patients. Our results in IEI and previous similar findings in healthy populations highlight that when assessing immune specific responses, the inclusion of CMV monitoring is suitable, worthwhile and may potentially be extended to vaccinations against different pathogens to prevent human disease more accurately.
Keywords: COVID-19, SARS-CoV-2, mRNA vaccines, inborn errors of immunity, IEI, Common Variable Immunodeficiency, CVID, CMV
Received: 03 Jul 2025; Accepted: 08 Sep 2025.
Copyright: © 2025 Alba-Cano, Alonso, Balastegui, Bravo-Gallego, Sánchez-Mateos, Martín-López and Gil-Herrera. 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: Juana Gil-Herrera, Division of Immunology. Hospital General Universitario "Gregorio Marañón", Madrid, Spain
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