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Clinical and Vaccine Immunology, November 2006, p. 1204-1211, Vol. 13, No. 11
1071-412X/06/$08.00+0     doi:10.1128/CVI.00195-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Generation of Mucosal Anti-Human Immunodeficiency Virus Type 1 T-Cell Responses by Recombinant Mycobacterium smegmatis{triangledown}

Jae-Sung Yu,1 James W. Peacock,1 Stacie Vanleeuwen,1 Tsungda Hsu,2 William R. Jacobs Jr.,2 Mark J. Cayabyab,3 Norman L. Letvin,3 Richard Frothingham,1 Herman F. Staats,1 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 30 May 2006/ Returned for modification 16 July 2006/ Accepted 20 August 2006

A successful vaccine vector for human immunodeficiency virus type 1 (HIV-1) should induce anti-HIV-1 immune responses at mucosal sites. We have generated recombinant Mycobacterium smegmatis vectors that express the HIV-1 group M consensus envelope protein (Env) as a surface, intracellular, or secreted protein and have tested them in animals for induction of both anti-HIV-1 T-cell and antibody responses. Recombinant M. smegmatis engineered for expression of secreted protein induced optimal T-cell gamma interferon enzyme-linked immunospot assay responses to HIV-1 envelope in the spleen, female reproductive tract, and lungs. Unlike with the induction of T-cell responses, priming and boosting with recombinant M. smegmatis did not induce anti-HIV-1 envelope antibody responses, due primarily to insufficient protein expression of the insert. However, immunization with recombinant M. smegmatis expressing HIV-1 Env was able to prime for an HIV-1 Env protein boost for the induction of anti-HIV-1 antibody responses.

* Corresponding author. Mailing address: P.O. Box 3258, Duke University Medical Center, 215 CARL 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 30 August 2006.

Clinical and Vaccine Immunology, November 2006, p. 1204-1211, Vol. 13, No. 11
1071-412X/06/$08.00+0     doi:10.1128/CVI.00195-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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