Journal of translational medicine · 2011
Definition of the viral targets of protective HIV-1-specific T cell responses.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Mothe Beatriz, Llano Anuska, Ibarrondo Javier, Daniels Marcus, Miranda Cristina, Zamarreño Jennifer, Bach Vanessa, Zuniga Rosario, Pérez-Álvarez Susana, Berger Christoph T, Puertas Maria C, Martinez-Picado Javier, Rolland Morgane, Farfan Marilu, Szinger James J, Hildebrand William H, Yang Otto O, Sanchez-Merino Victor, Brumme Chanson J, Brumme Zabrina L, Heckerman David, Allen Todd M, Mullins James I, Gómez Guadalupe, Goulder Philip J, Walker Bruce D, Gatell Jose M, Clotet Bonaventura, Korber Bette T, Sanchez Jorge, Brander Christian
Аннотация
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.
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.