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

Autor: Bruce D. Walker, Beatriz Mothe, Jorge Sanchez, Vanessa Bach, Philip J. R. Goulder, James J. Szinger, Otto O. Yang, Chanson J. Brumme, William H. Hildebrand, Christoph Berger, Victor Sanchez-Merino, Todd M. Allen, Zabrina L. Brumme, Cristina Miranda, Bonaventura Clotet, Rosario Zuñiga, Morgane Rolland, David Heckerman, F. Javier Ibarrondo, Anuska Llano, Susana Pérez-Álvarez, Guadalupe Gómez, Bette T. Korber, José M. Gatell, Marilu Farfan, Marcus Daniels, Javier Martinez-Picado, James I. Mullins, Maria C. Puertas, Christian Brander, Jennifer Zamarreño
Přispěvatelé: 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
Rok vydání: 2011
Předmět:
Male
Biologia
HIV specific CTL
immune correlate
T-Lymphocytes
lcsh:Medicine
HIV Infections
Virus Replication
gag Gene Products
Human Immunodeficiency Virus
Epitope
Conserved sequence
Cohort Studies
0302 clinical medicine
Peru
HIV vaccine
Conserved Sequence
Medicine(all)
epitope
0303 health sciences
General Medicine
Viral Load
3. Good health
HLA
medicine.anatomical_structure
030220 oncology & carcinogenesis
vaccine immunogen design
Viral load
clade B
functional avidity
clade C
T cell
Human leukocyte antigen
Biology
General Biochemistry
Genetics and Molecular Biology
Genetic Heterogeneity
03 medical and health sciences
Species Specificity
stomatognathic system
medicine
Humans
Amino Acid Sequence
Alleles
92 Biology and other natural sciences::92C Physiological
cellular and medical topics [Classificació AMS]
030304 developmental biology
Matemàtiques i estadística::Estadística aplicada::Estadística biosanitària [Àrees temàtiques de la UPC]
Biochemistry
Genetics and Molecular Biology(all)
Research
lcsh:R
Histocompatibility Antigens Class I
Virology
stomatognathic diseases
CTL
Viral replication
Multivariate Analysis
Immunology
HIV-1
Peptides
entropy
Zdroj: UPCommons. Portal del coneixement obert de la UPC
Universitat Politècnica de Catalunya (UPC)
Recercat. Dipósit de la Recerca de Catalunya
instname
Journal of Translational Medicine
Mothe, Beatriz; Llano, Anuska; Ibarrondo, Javier; Daniels, Marcus; Miranda, Cristina; Zamarreño, Jennifer; et al.(2011). Definition of the viral targets of protective HIV-1-specific T cell responses. Journal of Translational Medicine, 9(1), 208. doi: http://dx.doi.org/10.1186/1479-5876-9-208. Retrieved from: http://www.escholarship.org/uc/item/91f1850c
Journal of Translational Medicine, Vol 9, Iss 1, p 208 (2011)
ISSN: 1479-5876
DOI: 10.1186/1479-5876-9-208
Popis: 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.
Databáze: OpenAIRE
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