Computational Design of Epitope-Enriched HIV-1 Gag Antigens with Preserved Structure and Function for Induction of Broad CD8⁺ T Cell Responses.

ABSTRACT: The partially protective phenotype observed in HIV-infected long-term-non-progressors is often associated with certain HLA alleles, thus indicating that cytotoxic T lymphocyte (CTL) responses play a crucial role in combating virus replication. However, both the vast variability of HIV and the HLA diversity impose a challenge on elicitation of broad and effective CTL responses. Therefore, we conceived an algorithm for the enrichment of CD8⁺ T cell epitopes in HIV's Gag protein, respecting functional preservation to enable cross-presentation. Experimentally identified epitopes were compared to a Gag reference sequence. Amino-acid-substitutions (AAS) were assessed for their impact on Gag's budding-function using a trained classifier that considers structural models and sequence con

SUBMITTER: Asbach B 

PROVIDER: S-EPMC6062507 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature