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

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Títol:	Definition of the viral targets of protective HIV-1-specific T cell responses
Autor:	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.
Altres autors/autores:	Universitat Politècnica de Catalunya. Departament d'Estadística i Investigació Operativa
Matèries:	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
Tipus de document:	Article
Descripció:	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.
Altres identificadors i accés:	Mothe, B. [et al.]. Definition of the viral targets of protective HIV-1-specific T cell responses. "Journal of translational medicine", 07 Desembre 2011, vol. 9, núm. 208, p. 1-48. 1479-5876 http://hdl.handle.net/2117/14410 10.1186/1479-5876-9-208
Disponible al dipòsit:	E-prints UPC
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