JVI Accepts, published online ahead of print on 18 March 2009

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J. Virol. doi:10.1128/JVI.02544-08
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Recombinant BCG prime-recombinant adenovirus boost vaccination in rhesus monkeys elicits robust polyfunctional SIV-specific T cell responses

Mark J. Cayabyab, Birgit Korioth-Schmitz, Yue Sun, Angela Carville, Harikrishnan Balachandran, Ayako Miura, Kevin R. Carlson, Adam P. Buzby, Barton F. Haynes, William R. Jacobs, and Norman L. Letvin^*

Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215; New England Primate Research Center, Harvard Medical School, Southborough, MA 01772; Duke University School of Medicine, Durham, North Carolina 27710; and the Department of Microbiology and Immunology, Howard Hughes Medical Institute, Albert Einstein College of Medicine, Bronx, New York 10461

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

While mycobacteria have been proposed as vaccine vectors because of their persistence and safety, little has been done systematically to optimize their immunogenicity in nonhuman primates. We successfully generated rBCG expressing SIV Gag and Pol as multigenic, non-integrating vectors, but rBCG expressing SIV Env was unstable. A dose and route determination study in rhesus monkeys revealed that intramuscular administration of rBCG was associated with local reactogenicity; whereas intravenous and intradermal administration of 10⁶ to 10⁸ cfu rBCG was well-tolerated. Following single or repeat rBCG inoculations, monkeys developed high frequency BCG PPD IFN ELISpot responses. However, those same animals developed only modest SIV-specific CD8⁺ T cell responses. Nevertheless, high frequency SIV-specific cellular responses were observed in the rBCG-primed monkeys following boosting with rAd5 expressing the SIV antigens. These cellular responses were of greater magnitude and more persistent than those generated after vaccination with rAd5 alone. The vaccine-elicited cellular responses were predominantly polyfunctional CD8⁺ T cells. These findings support the further exploration of mycobacteria as priming vaccine vectors.

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