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HIV-1 Nef-derived HTI epitopes are specific peptide sequences derived from the Negative Regulatory Factor (Nef) protein of HIV-1, integrated into the HIV T-cell Immunogen (HTI) design (Mothe et al., 2015). The HTI immunogen is engineered to include 16 highly conserved regions of the HIV-1 genome (Gag, Pol, Vif, and Nef) that are preferentially targeted by T-cells in individuals who naturally control the virus without antiretroviral therapy (Bailon et al., 2022). Nef itself is a critical virulence factor that promotes viral replication and immune evasion by downregulating cell-surface molecules like MHC-I and CD4 (Geyer et al., 2001). The Nef-derived segments within HTI are selected to avoid decoy regions and focus the immune response on functionally constrained parts of the protein where mutations would incur a high fitness cost. By targeting these specific Nef epitopes via therapeutic vaccines like MVA-HTI or DNA-HTI, the goal is to elicit robust CD4+ and CD8+ T-cell responses capable of suppressing viral rebound after the cessation of antiretroviral therapy (AELIX Therapeutics, 2023). This approach is a key component of functional cure strategies in HIV research, aiming to enhance the host's ability to recognize and eliminate HIV-infected cells.
Induction of polyfunctional CD4+ and CD8+ T-cell responses against conserved viral epitopes to suppress HIV-1 replication.
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