{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T22:36:19Z","timestamp":1787870179988,"version":"build-2784847793"},"reference-count":44,"publisher":"American Society for Clinical Investigation","issue":"21","license":[{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"crossref","award":["256073931,272983813,441891347,HO 5836\/2-1"],"award-info":[{"award-number":["256073931,272983813,441891347,HO 5836\/2-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Helmholtz Association\u2019s Initiative and Networking Fund","award":["KA1-Co-02 \u201cCOVIPA\u201d"],"award-info":[{"award-number":["KA1-Co-02 \u201cCOVIPA\u201d"]}]},{"DOI":"10.13039\/501100002347","name":"Federal Ministry of Education and Research","doi-asserted-by":"crossref","award":["01KX2121,NUM 2.0,01EO2103"],"award-info":[{"award-number":["01KX2121,NUM 2.0,01EO2103"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,10]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>\n                      Among people living with HIV (PLWH), immunological nonresponders (INR) fail to adequately restore CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cell counts despite effective antiretroviral therapy (ART), placing them at greater risk for adverse outcomes and reduced vaccine efficacy. We aimed to study the robustness and longevity of vaccine-induced virus-specific cellular immune responses in INR.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      Virus-specific CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell responses were analyzed in INR (CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cell count &lt; 300 cells\/\u03bcL) and immunological responders (IR) (CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cell count &gt; 500 cells\/\u03bcL), receiving ART, and HIV-uninfected controls following COVID-19 mRNA vaccination and infection. Virus-specific CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells were characterized using peptide-loaded MHC I tetramer technology, after in vitro expansion and cytokine production assays. Virus-specific CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells and IgG levels were determined by activation-induced marker (AIM) assay and ELISA, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      We demonstrated that, while long-lasting virus-specific cellular immune responses were generated in INR, CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell immunity remained limited compared with robust CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cell reactivity. CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell responses in INR exhibited reduced breadth and frequency, accompanied by altered memory differentiation and suboptimal activation and effector response upon antigen exposure. This deficiency correlated with low CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cell counts, independent of other disease markers, highlighting the pivotal role of CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells in orchestrating vaccine-induced immunity. Notably, repeated booster vaccinations enhanced virus-specific CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell responses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>\n                      INR elicit limited vaccine-induced virus-specific CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell immunity, but booster vaccinations can enhance these responses, suggesting better immune outcomes with tailored vaccination strategies.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>FUNDING<\/jats:title>\n                    <jats:p>Helmholtz Society, German Research Foundation, Federal Ministry of Education and Research.<\/jats:p>\n                  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