Definition of the viral targets of protective HIV-1-specific T cell responses
- Beatriz Mothe ,
- Anuska Llano ,
- Javier Ibarrondo ,
- Marcus Daniels ,
- Cristina Miranda ,
- Jennifer Zamarreno ,
- Vanessa Bach ,
- Rosario Zuniga ,
- Susana Perez-Alvarez ,
- Chirstoph T. Berger ,
- Maria C. Puertas ,
- Javier Martinez-Picado ,
- Morgane Rolland ,
- Marilu Farfan ,
- James J. Szinger ,
- William H. Hildebrand ,
- Otto O. Yang ,
- Victor Sanchez-Merino ,
- Chanson J. Brumme ,
- Zabrina L. Brumme ,
- David Heckerman ,
- Todd M. Allen ,
- James I. Mullins ,
- Guadalupe Gomez ,
- Philip J. Goulder ,
- Bruce D. Walker ,
- Jose M. Gatell ,
- Bonaventura Clotet ,
- Better T. Korber ,
- Jorge Sanchez ,
- Chirstian Brander
Journal of Translational Medicine | , Vol 9(208)
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.