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J. Virol. doi:10.1128/JVI.02616-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Magnitude and Phenotype of Cellular Immune Responses Elicited by Recombinant Adenovirus Vectors and Heterologous Prime-Boost Regimens in Rhesus Monkeys

Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215; Crucell Holland BV, 2301 CA, Leiden, The Netherlands; New England Primate Research Center, Southborough, MA 01772

^* To whom correspondence should be addressed. Email: dbarouch{at}bidmc.harvard.edu.

	Abstract

Recombinant adenovirus serotype 5 (rAd5) vaccine vectors for HIV-1 and other pathogens have been shown to elicit antigen-specific cellular immune responses. Rare serotype rAd vectors have also been constructed to circumvent pre-existing anti-Ad5 immunity and to facilitate the development of novel heterologous rAd prime-boost regimens. Here we show that rAd5, rAd26, and rAd48 vectors elicit qualitatively distinct phenotypes of cellular immune responses in rhesus monkeys and can be combined as potent heterologous prime-boost vaccine regimens. While rAd5-Gag induced primarily IFN-+ and IFN-+/TNF-+ T lymphocyte responses, rAd26-Gag and rAd48-Gag induced higher proportions of IL-2+ and polyfunctional IFN-+/TNF-+/IL-2+ T lymphocyte responses. Priming with the rare serotype rAd vectors proved remarkably effective for subsequent boosting with rAd5 vectors. These data demonstrate that the rare serotype rAd vectors elicited phenotypically distinct T lymphocyte responses as compared with rAd5 vectors and suggest the functional relevance of polyfunctional CD8+ and CD4+ T lymphocyte responses. Moreover, qualitative differences in cellular immune responses may prove critical in determining the overall potency of heterologous rAd prime-boost regimens.

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