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BACKGROUND: The efficacy of the CTL component of a future HIV-1 vaccine will depend on the induction of responses with the most potent antiviral activity and broad HLA class I restriction. However, current HIV vaccine designs are largely based on viral sequence alignments only, not incorporating experimental data on T cell function and specificity. METHODS: Here, 950 untreated HIV-1 clade B or -C infected individuals were tested for responses to sets of 410 overlapping peptides (OLP) spanning the entire HIV-1 proteome. For each OLP, a "protective ratio" (PR) was calculated as the ratio of median viral loads (VL) between OLP non-responders and responders. RESULTS: For both clades, there was a negative relationship between the PR and the entropy of the OLP sequence. There was also a significant additive effect of multiple responses to beneficial OLP. Responses to beneficial OLP were of significantly higher functional avidity than responses to non-beneficial OLP. They also had superior in-vitro antiviral activities and, importantly, were at least as predictive of individuals' viral loads than their HLA class I genotypes. CONCLUSIONS: The data thus identify immunogen sequence candidates for HIV and provide an approach for T cell immunogen design applicable to other viral infections.

Original publication

DOI

10.1186/1479-5876-9-208

Type

Journal article

Journal

J Transl Med

Publication Date

07/12/2011

Volume

9

Keywords

Alleles, Amino Acid Sequence, Cohort Studies, Conserved Sequence, Genetic Heterogeneity, HIV Infections, HIV-1, Histocompatibility Antigens Class I, Humans, Male, Multivariate Analysis, Peptides, Peru, Species Specificity, T-Lymphocytes, Viral Load, Virus Replication, gag Gene Products, Human Immunodeficiency Virus