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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; Universitat Politècnica de Catalunya. GREMA - Grup de Recerca en Estadística Matemàtica i les seves Aplicacions
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.
Peer Reviewed
Postprint (published version)
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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