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HLA-II-Associated HIV-1 Adaptation Decreases CD4 + T-Cell Responses in HIV-1 Vaccine Recipients

Files, J.K., Sterrett, S., Henostroza, S., Fucile, C., Maroney, K., Fram, T., Mallal, S., Kalams, S., Carlson, J., Rosenberg, A., Erdmann, N., Bansal, A., Goepfert, P.A. and Silvestri, G. (2022) HLA-II-Associated HIV-1 Adaptation Decreases CD4 + T-Cell Responses in HIV-1 Vaccine Recipients. Journal of Virology .

Link to Published Version: https://doi.org/10.1128/jvi.01191-22
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Abstract

Epitopes with evidence of HLA-II-associated adaptation induce poorly immunogenic CD4+ T-cell responses in HIV-positive (HIV+) individuals. Many such escaped CD4+ T-cell epitopes are encoded by HIV-1 vaccines being evaluated in clinical trials. Here, we assessed whether this viral adaptation adversely impacts CD4+ T-cell responses following HIV-1 vaccination, thereby representing escaped epitopes. When evaluated in separate peptide pools, vaccine-encoded adapted epitopes (AE) induced CD4+ T-cell responses less frequently than nonadapted epitopes (NAE). We also demonstrated that in a polyvalent vaccine, where both forms of the same epitope were encoded, AE were less immunogenic. NAE-specific CD4+ T cells had increased, albeit low, levels of interferon gamma (IFN-γ) cytokine production. Single-cell transcriptomic analyses showed that NAE-specific CD4+ T cells expressed interferon-related genes, while AE-specific CD4+ T cells resembled a Th2 phenotype. Importantly, the magnitude of NAE-specific CD4+ T-cell responses, but not that of AE-specific responses, was found to positively correlate with Env-specific antibodies in a vaccine efficacy trial. Together, these findings show that HLA-II-associated viral adaptation reduces CD4+ T-cell responses in HIV-1 vaccine recipients and suggest that vaccines encoding a significant number of AE may not provide optimal B-cell help for HIV-specific antibody production.

Item Type: Journal Article
Murdoch Affiliation(s): Institute for Immunology and Infectious Diseases
Publisher: American Society for Microbiology
Copyright: © 2022 American Society for Microbiology
URI: http://researchrepository.murdoch.edu.au/id/eprint/65934
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