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Título:	Definition of the viral targets of protective HIV-1-specific T cell responses
Autor/a:	Pérez-Alvarez, Susana; Mothe, Beatriz; Llano, Anuska; Ibarrondo, Javier; Daniels, Marcus; Miranda, Cristina; Zamarreño, Jennifer; Bach, Vanessa; Zuniga, Rosario; Brander, C.; Sanchez, Jorge; Brumme, Chanson J.; Sánchez-Merino, Victor; Yang, Otto O.; Hildebrand, William H.; Szinger, James J.; Farfan, Marilu; Rolland, Morgane; Martínez-Picado, Javier; Puertas, Maria C.; Berger, Chistoph T.; Brumme, Zabrina L.; Korber, Bette T.; Gatell, Jose M.; Clotet, Bonaventura; Goulder, Philip J.; Walker, Bruce D.; Mullins, James I.; Gómez Melis, Guadalupe; Heckerman, David; Allen, Todd M.
Otros autores:	Universitat Politècnica de Catalunya. Departament d'Estadística i Investigació Operativa; Universitat Politècnica de Catalunya. GREMA - Grup de Recerca en Estadística Matemàtica i les seves Aplicacions
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 nonresponders 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.
Abstract:	Peer Reviewed
Materia(s):	-Àrees temàtiques de la UPC::Matemàtiques i estadística::Estadística aplicada::Estadística biosanitària -Biology -epitope -entropy -immune correlate. -HIV specific CTL -clade B -clade C -HLA -vaccine immunogen design -functional avidity -Biologia -Classificació AMS::92 Biology and other natural sciences::92C Physiological, cellular and medical topics
Derechos:	Attribution-NonCommercial-NoDerivs 3.0 Spain http://creativecommons.org/licenses/by-nc-nd/3.0/es/
Tipo de documento:	Artículo - Versión publicada Artículo
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