{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T08:52:29Z","timestamp":1777711949969,"version":"3.51.4"},"reference-count":77,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T00:00:00Z","timestamp":1759190400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The immunogenicity of mRNA COVID-19 vaccines has been reported as highly variable in patients with inborn errors of immunity (IEI).<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>The aim of this study was to study memory CD4<jats:sup>+<\/jats:sup> T-cell-mediated responses against the Spike (S) protein of SARS-CoV-2 along with CMV peptides in a large IEI group composed of mostly predominantly antibody-deficient (PAD) patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and methods<\/jats:title><jats:p><jats:italic>In vitro<\/jats:italic> antigen-specific T-cell anti-S and -CMV responses after two doses of mRNA COVID-19 vaccines were assessed in peripheral blood from 114 patients with IEI and 38 healthcare healthy controls (HCHC). Stimulation index (SI) based on the percentages of CD4<jats:sup>+<\/jats:sup> T lymphocytes with effector memory phenotype CD45RA<jats:sup>\u2212<\/jats:sup>CD27<jats:sup>\u2212<\/jats:sup> (TEM) was quantified by flow cytometry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Patients with IEI 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>CMV latency negatively impacted the CD4<jats:sup>+<\/jats:sup> TEM population\u2019s functionality regarding COVID-19 vaccination in patients with CVID. Our results in patients with IEI and previous similar findings in healthy populations highlight the fact that when assessing immune-specific responses, the inclusion of CMV monitoring is suitable, is worthwhile, and may potentially be extended to vaccinations against different pathogens to prevent human disease more accurately.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1659259","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T05:32:43Z","timestamp":1759210363000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Impact of CMV latency on T-cell responses to COVID-19 vaccination among predominantly antibody-deficient 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