Reche, Pedro A.Keskin, Derin BenerciHussey, RebeccaAncuta, PetronelaGabuzda, DanaReinherz, Ellis2011-03-022006Reche, Pedro A., Derin B. Keskin, Rebecca E. Hussey, Petronela Ancuta, Dana Gabuzda, and Ellis L. Reinherz. 2006. Elicitation from virus-naive individuals of cytotoxic T lymphocytes directed against conserved HIV-1 epitopes. Medical Immunology 5: 1.1476-9433http://nrs.harvard.edu/urn-3:HUL.InstRepos:4734540Cytotoxic 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 IFNγ producing cells and mount anti-HIV-1 cytolytic activity. This disparity suggests a vaccine design paradigm shift from infected to normal subjects.en-USJournal Article2011-03-0210.1186/1476-9433-5-1