期刊
JOURNAL OF TRANSLATIONAL MEDICINE
卷 9, 期 -, 页码 -出版社
BMC
DOI: 10.1186/1479-5876-9-208
关键词
HIV specific CTL; clade B; clade C; HLA; vaccine immunogen design; functional avidity; epitope; entropy; immune correlate
资金
- NIH [N01-AI-30024, N01-AI-15422]
- NIH-NIDCR [R01 DE018925-04]
- Ministerio de Ciencia y Tecnologia [MTM2008-06747-C02-00]
- Instituto de Salud Carlos III [FIS PS09/00283]
- Fundacio para la Investigacion y Prevencion del SIDA en Espana (FIPSE) [360737/09]
- European Community
- FIS (Rio Hortega, Madrid, Spain) [CM08/00020]
- Canadian Institutes of Health Research (CIHR)
- ICREA Funding Source: Custom
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.
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