Definition of the viral targets of protective HIV-1-specific T cell responses

Definition of the viral targets of protective HIV-1-specific T cell responses

Online publication: 07/12/2011 Journal: Journal of Translational Medicine

Abstract:

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.

Authors: Mothe B, Llano A, Ibarrondo J, Daniels M, Miranda C, Zamarreño J, Bach V, Zuniga R, Pérez-Álvarez S, Berger CT, Puertas MC, Martinez-Picado J, Rolland M, Farfan M, Szinger JJ, Hildebrand WH, Yang OO, Sanchez-Merino V, Brumme CJ, Brumme ZL, Heckerman D, Allen TM, Mullins JI, Gómez G, Goulder PJ, Walker BD, Gatell JM, Clotet B, Korber BT, Sanchez J, Brander C.

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