Elicitation of high-frequency cytotoxic T-lymphocyte responses against both dominant and subdominant simian-human immunodeficiency virus epitopes by DNA vaccination of rhesus monkeys |
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Authors: | Barouch D H Craiu A Santra S Egan M A Schmitz J E Kuroda M J Fu T M Nam J H Wyatt L S Lifton M A Krivulka G R Nickerson C E Lord C I Moss B Lewis M G Hirsch V M Shiver J W Letvin N L |
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Institution: | Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA. dan_barouch@hotmail.com |
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Abstract: | Increasing evidence suggests that the generation of cytotoxic T-lymphocyte (CTL) responses specific for a diversity of viral epitopes will be needed for an effective human immunodeficiency virus type 1 (HIV-1) vaccine. Here, we determine the frequencies of CTL responses specific for the simian immunodeficiency virus Gag p11C and HIV-1 Env p41A epitopes in simian-human immunodeficiency virus (SHIV)-infected and vaccinated rhesus monkeys. The p11C-specific CTL response was high frequency and dominant and the p41A-specific CTL response was low frequency and subdominant in both SHIV-infected monkeys and in monkeys vaccinated with recombinant modified vaccinia virus Ankara vectors expressing these viral antigens. Interestingly, we found that plasmid DNA vaccination led to high-frequency CTL responses specific for both of these epitopes. These data demonstrate that plasmid DNA may be useful in eliciting a broad CTL response against multiple epitopes. |
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