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Journal of Virology, March 1999, p. 1853-1859, Vol. 73, No. 3
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Acute Effects of Pathogenic Simian-Human Immunodeficiency Virus Challenge on Vaccine-Induced Cellular and Humoral Immune Responses to Gag in Rhesus Macaquesdagger

Krista K. Steger,Dagger Paul M. Waterman, and C. David Pauza*

Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, and Wisconsin Regional Primate Research Center, Madison, Wisconsin 53706

Received 9 October 1998/Accepted 9 December 1998

Simian-human immunodeficiency virus (SHIV) infection in macaques provides a convenient model for testing vaccine efficacy and for understanding viral pathogenesis in AIDS. We immunized macaques with recombinant, Salmonella typhimurium (expressing Gag) or soluble Gag in adjuvant to generate T-cell-dependent lymphoproliferative or serum antibody responses. Immunized animals were challenged by intrarectal inoculation with SHIV89.6PD. Virus infection was accompanied by rapid losses of lymphoproliferative responses to Gag or phytohemagglutinin. By 8 weeks, mitogen responses recovered to near normal levels but antigen-specific immunity remained at low or undetectable levels. Serum antibody levels were elevated initially by virus exposure but soon dropped well below levels achieved by immunization. Our studies show a rapid depletion of preexisting Gag-specific CD4+ T cells that prevent or limit subsequent antiviral cellular and humoral immune responses during acute SHIV infection.

* Corresponding author. Mailing address: Department of Pathology, University of Wisconsin, 1300 University Ave., Madison, WI 53706. Phone: (608) 262-9147. Fax: (608) 262-9148. E-mail: cdpauza{at}facstaff.wisc.edu.

dagger Manuscript 38-023 from the Wisconsin Regional Primate Research Center.

Dagger Present address: Section of Comparative Medicine, Yale University, New Haven, CT 06520-8016.

Journal of Virology, March 1999, p. 1853-1859, Vol. 73, No. 3
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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