Research
Definition of the viral targets of protective HIV-1-specific T cell responses
1 Irsicaixa AIDS Research Institute-HIVACAT, Badalona, Spain
2 'Lluita contra la SIDA' Foundation, Hospital Germans Trias i Pujol, Badalona, Spain
3 Universitat Autònoma de Barcelona, Barcelona, Spain
4 Los Alamos National Laboratory, Los Alamos, NM, USA
5 Asociación Civil IMPACTA Salud y Educacion, Lima, Peru
6 Dept. Estadística i Investigació Operativa, Universitat Politècnica de Catalunya, Barcelona, Spain
7 Ragon Institute of MGH, Harvard and MIT, Boston, MA, USA
8 Institucio Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain
9 MHRP, Frederick, USA
10 University of Oklahoma Medical Center, Oklahoma City, OK, USA
11 University of California, Los Angeles, CA, USA
12 Services of Immunology and Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS)-AIDS Research Group-HIVACAT, Hospital Clinic, Barcelona, Spain
13 British Columbia Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada
14 Simon Fraser University, Burnaby, BC, Canada
15 Miscrosoft Research, Redmond, WA, USA
16 Department of Microbiology, University of Washington, Seattle, WA, USA
17 Department of Paediatrics, Nuffield Department of Medicine, Oxford, UK
18 University of KwaZulu-Natal, HIV Pathogenesis Program, DDMRI, Durban, South Africa
19 Howard Hughes Medical Institute, Chevy Chase, MD, USA
20 Santa Fe Institute, Santa Fe, NM, USA
Journal of Translational Medicine 2011, 9:208 doi:10.1186/1479-5876-9-208
Published: 7 December 2011Abstract
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.
