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oai:recercat.cat:2117/144102026-02-09T06:16:03Zcom_2072_1033col_2072_452950

Definition of the viral targets of protective HIV-1-specific T cell responses 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. 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 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 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. Peer Reviewed Postprint (published version) 2011-12-07 Article 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 https://hdl.handle.net/2117/14410 10.1186/1479-5876-9-208 22152067 eng http://www.translational-medicine.com/content/pdf/1479-5876-9-208.pdf http://creativecommons.org/licenses/by-nc-nd/3.0/es/ Open Access Attribution-NonCommercial-NoDerivs 3.0 Spain 48 p. application/pdf