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J. Virol. doi:10.1128/JVI.01269-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Rapid memory CD8⁺ T lymphocyte induction through priming with recombinant Mycobacterium smegmatis

Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115; Duke University School of Medicine, Durham, NC 27710. Howard Hughes Medical Institute, Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461

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

	Abstract

The most promising vaccine strategies for induction of cytotoxic T lymphocyte responses have been heterologous prime/boost regimens employing a plasmid DNA prime and a live recombinant vector boost. The priming immunogen in these regimens must elicit antigen-specific memory CD8⁺ T lymphocytes that will expand following the boosting immunization. Because plasmid DNA immunogens are expensive and their immunogenicity has proven disappointing in human clinical trials, we have been exploring novel priming immunogens that might be used in heterologous immunization regimens. Here we show that priming with a prototype recombinant Mycobacterium smegmatis expressing HIV-1 gp120 elicited CD4⁺ T lymphocytes with a functional profile of helper cells as well as a CD8⁺ T lymphocyte population. These CD8⁺ T lymphocytes rapidly differentiated to memory cells, defined on the basis of their cytokine profile and expression of CD62L and CD27. Moreover, these recombinant mycobacteria-induced T lymphocytes rapidly expanded following boosting with a recombinant adenovirus expressing HIV-1 env to gp120-specific CD8⁺ T lymphocytes. This work demonstrates a remarkable skewing of recombinant mycobacterium-induced T lymphocytes to durable antigen-specific memory CD8⁺ T cells, and suggests that such immunogens might be used as priming vectors in prime/boost vaccination regimens for the induction of cellular immune responses.

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