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Journal of Virology, February 2006, p. 1645-1652, Vol. 80, No. 4
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.4.1645-1652.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Generation of CD8+ T-Cell Responses by a Recombinant Nonpathogenic Mycobacterium smegmatis Vaccine Vector Expressing Human Immunodeficiency Virus Type 1 Env

Mark J. Cayabyab,1 Avi-Hai Hovav,1 Tsungda Hsu,2 Georgia R. Krivulka,1 Michelle A. Lifton,1 Darci A. Gorgone,1 Glenn J. Fennelly,3 Barton F. Haynes,4 William R. Jacobs Jr.,2 and Norman L. Letvin1*

Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215,1 Department of Microbiology and Immunology, Howard Hughes Medical Institute,2 Department of Pediatrics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461,3 Duke University School of Medicine, Durham, North Carolina 277104

Received 25 August 2005/ Accepted 30 November 2005

Because the vaccine vectors currently being evaluated in human populations all have significant limitations in their immunogenicity, novel vaccine strategies are needed for the elicitation of cell-mediated immunity. The nonpathogenic, rapidly growing mycobacterium Mycobacterium smegmatis was engineered as a vector expressing full-length human immunodeficiency virus type 1 (HIV-1) HXBc2 envelope protein. Immunization of mice with recombinant M. smegmatis led to the expansion of major histocompatibility complex class I-restricted HIV-1 epitope-specific CD8+ T cells that were cytolytic and secreted gamma interferon. Effector and memory T lymphocytes were elicited, and repeated immunization generated a stable central memory pool of virus-specific cells. Importantly, preexisting immunity to Mycobacterium bovis BCG had only a marginal effect on the immunogenicity of recombinant M. smegmatis. This mycobacterium may therefore be a useful vaccine vector.

* Corresponding author. Mailing address: Department of Medicine, Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave., Boston, MA 02130. Phone: (617) 667-2042. Fax: (617) 667-8210. E-mail: nletvin{at}bidmc.harvard.edu.

Journal of Virology, February 2006, p. 1645-1652, Vol. 80, No. 4
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.4.1645-1652.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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