Elicitation from virus-naive individuals of cytotoxic T lymphocytes directed against conserved HIV-1 epitopes

Reche Gallardo, Pedro Antonio; Keskin, Derin B; Hussey, Rebecca E; Ancuta, Petronela; Gabuzda, Dana; Reinherz, Ellis L

Elicitation from virus-naive individuals of cytotoxic T lymphocytes directed against conserved HIV-1 epitopes

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31.Reche_etal_MI_2006.pdf (658.15 KB)

Official URL

http://www.medimmunol.com/content/5/1/1

Publication date

2006

Authors

Reche Gallardo, Pedro Antonio

Publisher

BioMed Central

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URI

https://hdl.handle.net/20.500.14352/50380

Abstract

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.