Journal article
HLA-II-Associated HIV-1 Adaptation Decreases CD4 + T-Cell Responses in HIV-1 Vaccine Recipients
Journal of Virology, Vol.96(17)
2022
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.
Details
- Title
- HLA-II-Associated HIV-1 Adaptation Decreases CD4 + T-Cell Responses in HIV-1 Vaccine Recipients
- Authors/Creators
- J.K. Files (Author/Creator)S. Sterrett (Author/Creator)S. Henostroza (Author/Creator)C. Fucile (Author/Creator)K. Maroney (Author/Creator)T. Fram (Author/Creator)S. Mallal (Author/Creator)S. Kalams (Author/Creator)J. Carlson (Author/Creator)A. Rosenberg (Author/Creator)N. Erdmann (Author/Creator)A. Bansal (Author/Creator)P.A. Goepfert (Author/Creator)G. Silvestri (Author/Creator)
- Publication Details
- Journal of Virology, Vol.96(17)
- Publisher
- American Society for Microbiology
- Identifiers
- 991005544273207891
- Copyright
- © 2022 American Society for Microbiology
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.66 HIV
- 1.66.46 HIV Pathogenesis
- Web Of Science research areas
- Virology
- ESI research areas
- Microbiology