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Enhancement of viral escape in HIV-1 Nef by STEP vaccination.


ABSTRACT: Properly priming cytotoxic T-lymphocyte (CTL) responses is an important task in HIV-1 vaccination. However, the STEP trial showed no efficacy even though the vaccine elicited HIV-specific CTL responses. Our study is to investigate whether or not the STEP vaccine enhanced viral escape in infected volunteers.The signature of viral escape, the presence of multiple escape variants, could be falsely represented by the existence of multiple founder viruses. Therefore, we use a mathematical model to designate STEP study patients with infections from a single founder virus. We then conduct permutation tests on each of 9988 Gag, Pol, and Nef overlapping peptides to identify epitopes with significant differences in diversity between the vaccine and placebo groups using previously published STEP trial sequence data.We identify signatures of vaccine-enhanced viral escape within HIV-1 Nef from the STEP trial. Vaccine-treated patients showed a greater level of epitope diversity in one of the immunodomiant epitopes, EVGFPVRPQVPL (Nef65-76), compared with placebo-treated patients (P?=?0.0038). In the other three Nef epitopes, there is a marginally significant difference in the epitope diversity between the vaccine and placebo group (P?

PROVIDER: S-EPMC5051524 | BioStudies |

REPOSITORIES: biostudies

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