This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A major barrier to developing an effective vaccine against HIV is the very high inter- and intra-clade diversity of HIV-1. Here, we evaluated the magnitude and breadth of cross-clade CD4 and CD8 T cell responses elicited by a DNA/MVA HIV-1 clade B vaccine in macaques using small pools of overlapping Gag peptides specific to our clade B and our recombinant AG vaccines. Identified epitopes were partially mapped, compared against their respective viral sequences to confirm the authenticity of cross-clade activity, and analyzed for their conservation among all known HIV-1 isolates for which the Gag protein sequences are available in the HIV Molecular Immunology database at the Los Alamos National Laboratory (LANL). Finally, we searched the LANL database for the conservation of the identified epitopes between macaques and humans. The cross-clade activity for the AG sequence was better conserved for CD8 than CD4 T cells. CD8 T cells exhibited 75% conservation for height and 83% conservation for breadth, whereas CD4 responses exhibited 45% conservation for height and 50% conservation for breadth. Five CD8 epitopes and 8 CD4 Epitopes were mapped. Three of the 5 CD8 epitopes and 2 of the 8 CD4 epitopes were conserved across multiple HIV-1 clades. Impressively, all of the CD8 epitopes, and half of the CD4 epitopes, have been reported for human infections. A study in macaques has been initiated to test the immunogenicity of the clinical lots of the DNA and MVA vaccines that will be used in the clinical trial of our clade B HIV-1 vaccine. Assays on the T and B cell responses elicited by the vaccine are being conducted under GLP conditions.
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