%0 Journal Article
%A Reche Gallardo, Pedro Antonio
%A Keskin, Derin B
%A Hussey, Rebecca E
%A Ancuta, Petronela
%A Gabuzda, Dana
%A Reinherz, Ellis L
%T Elicitation from virus-naive individuals of cytotoxic T lymphocytes directed against conserved HIV-1 epitopes
%D 2006
%@ 1476-9433
%U https://hdl.handle.net/20.500.14352/50380
%X Cytotoxic T lymphocytes (CTL) protect against viruses including HIV-1. To avoid viral escape mutants that thwart immunity, we chose 25 CTL epitopes defined in the context of natural infection with functional and/or structural constraints that maintain sequence conservation. By combining HLA binding predictions with knowledge concerning HLA allele frequencies, a metric estimating population protection coverage (PPC) was computed and epitope pools assembled. Strikingly, only a minority of immunocompetent HIV-1 infected individuals responds to pools with PPC >95%. In contrast, virus-naive individuals uniformly expand IFNgamma producing cells and mount anti-HIV-1 cytolytic activity. This disparity suggests a vaccine design paradigm shift from infected to normal subjects.
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