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Journal of Virology, April 2002, p. 3800-3809, Vol. 76, No. 8
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.8.3800-3809.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Outcome of Simian-Human Immunodeficiency Virus Strain 89.6p Challenge following Vaccination of Rhesus Macaques with Human Immunodeficiency Virus Tat Protein

Peter Silvera,1* Max W. Richardson,2 Jack Greenhouse,1 Jake Yalley-Ogunro,1 Nigel Shaw,1 Jyotika Mirchandani,2 Kamel Khalili,2 Jean-Francois Zagury,3 Mark G. Lewis,1 and Jay Rappaport2

Southern Research Institute, Frederick, Maryland,1 Temple University, Philadelphia, Pennsylvania,2 Université Pierre et Marie Curie, Paris, France3

Received 29 November 2001/ Accepted 16 January 2002

The regulatory proteins Nef, Rev, and Tat of human immunodeficiency virus type 1 (HIV-1) are attractive targets for vaccine development, since induction of effective immune responses targeting these early proteins may best control virus replication. Here we investigated whether vaccination with biologically active Tat or inactive Tat toxoid derived from HIV-1IIIB and simian-human immunodeficiency virus (SHIV) strain 89.6p would induce protective immunity in rhesus macaques. Vaccination induced high titers of anti-Tat immunoglobulin G in all immunized animals by week 7, but titers were somewhat lower in the 89.6p Tat group. Dominant B-cell epitopes mapped to the amino terminus, the basic domain, and the carboxy-terminal region. Tat-specific T-helper responses were detected in 50% of immunized animals. T-cell epitopes appeared to map within amino acids (aa) 1 to 24 and aa 37 to 66. In addition, Tat-specific gamma interferon responses were detected in CD4+ and/or CD8+ T lymphocytes in 11 of 16 immunized animals on the day of challenge. However, all animals became infected upon intravenous challenge with 30 50% minimal infective doses of SHIV 89.6p, and there were no significant differences in viral loads or CD4+ T-cell counts between immunized and control animals. Thus, vaccination with HIV-1IIIB or SHIV 89.6p Tat or with Tat toxoid preparations failed to confer protection against SHIV 89.6p infection despite robust Tat-specific humoral and cellular immune responses in some animals. Given its apparent immunogenicity, Tat may be more effective as a component of a cocktail vaccine in combination with other regulatory and/or structural proteins of HIV-1.

* Corresponding author. Mailing address: Infectious Disease Research, Southern Research Institute, 431 Aviation Way, Frederick, MD 21701. Phone: (301) 694-3232. Fax: (301) 694-7223. E-mail: silvera{at}sri.org.

Journal of Virology, April 2002, p. 3800-3809, Vol. 76, No. 8
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.8.3800-3809.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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