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Limited vaccine-induced CD8+ T cell immunity in HIV-infected immunological nonresponders
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Limited vaccine-induced CD8+ T cell immunity in HIV-infected immunological nonresponders
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Journal Article
Limited vaccine-induced CD8+ T cell immunity in HIV-infected immunological nonresponders
2025
Overview
BACKGROUNDAmong people living with HIV (PLWH), immunological nonresponders (INR) fail to adequately restore CD4+ 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.METHODSVirus-specific CD8+ T cell responses were analyzed in INR (CD4+ T cell count < 300 cells/μL) and immunological responders (IR) (CD4+ T cell count > 500 cells/μL), receiving ART, and HIV-uninfected controls following COVID-19 mRNA vaccination and infection. Virus-specific CD8+ T cells were characterized using peptide-loaded MHC I tetramer technology, after in vitro expansion and cytokine production assays. Virus-specific CD4+ T cells and IgG levels were determined by activation-induced marker (AIM) assay and ELISA, respectively.RESULTSWe demonstrated that, while long-lasting virus-specific cellular immune responses were generated in INR, CD8+ T cell immunity remained limited compared with robust CD4+ T cell reactivity. CD8+ 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+ T cell counts, independent of other disease markers, highlighting the pivotal role of CD4+ T cells in orchestrating vaccine-induced immunity. Notably, repeated booster vaccinations enhanced virus-specific CD8+ T cell responses.CONCLUSIONINR elicit limited vaccine-induced virus-specific CD8+ T cell immunity, but booster vaccinations can enhance these responses, suggesting better immune outcomes with tailored vaccination strategies.FUNDINGHelmholtz Society, German Research Foundation, Federal Ministry of Education and Research.
Publisher
American Society for Clinical Investigation
