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Clinical and Vaccine Immunology, July 2007, p. 886-893, Vol. 14, No. 7
1071-412X/07/$08.00+0     doi:10.1128/CVI.00407-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Recombinant Mycobacterium bovis Bacillus Calmette-Guérin Elicits Human Immunodeficiency Virus Type 1 Envelope-Specific T Lymphocytes at Mucosal Sites{triangledown}

Jae-Sung Yu,1,{dagger} James W. Peacock,1,{dagger} William R. Jacobs Jr.,2 Richard Frothingham,1 Norman L. Letvin,3 Hua-Xin Liao,1 and Barton F. Haynes1*

Human Vaccine Institute and Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710,1 Howard Hughes Medical Institute and Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461,2 Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 022153

Received 2 October 2006/ Returned for modification 12 March 2007/ Accepted 9 May 2007

A successful vaccine vector for human immunodeficiency virus type 1 (HIV-1) should induce anti-HIV-1 T-cell immune responses at mucosal sites. We have constructed recombinant Mycobacterium bovis bacillus Calmette-Guérin (rBCG) expressing an HIV-1 group M consensus envelope (Env) either as a surface, intracellular, or secreted protein as an immunogen. rBCG containing HIV-1 env plasmids engineered for secretion induced optimal Env-specific T-cell gamma interferon enzyme-linked immunospot responses in murine spleen, female reproductive tract, and lungs. While rBCG-induced T-cell responses to HIV-1 envelope in spleen were lower than those induced by adenovirus prime/recombinant vaccinia virus (rAd-rVV) boost, rBCG induced comparable responses to rAd-rVV immunization in the female reproductive tract and lungs. T-cell responses induced by rBCG were primarily CD4+, although rBCG alone did not induce anti-HIV-1 antibody. However, rBCG could prime for a protein boost by HIV-1 envelope protein. Thus, rBCG can serve as a vector for induction of anti-HIV-1 consensus Env cellular responses at mucosal sites.

* Corresponding author. Mailing address: P.O. Box 103020, Duke University Medical Center, 4090 MSRBII Building, Research Drive, Durham, NC 27710. Phone: (919) 684-5384. Fax: (919) 681-8992. E-mail: hayne002{at}mc.duke.edu

{triangledown} Published ahead of print on 16 May 2007.

{dagger} These authors contributed equally.

Clinical and Vaccine Immunology, July 2007, p. 886-893, Vol. 14, No. 7
1071-412X/07/$08.00+0     doi:10.1128/CVI.00407-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





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