Acute effects of pathogenic simian-human immunodeficiency virus challenge on vaccine-induced cellular and humoral immune responses to Gag in rhesus macaques.
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.
Steger
K K
KK
Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, and Wisconsin Regional Primate Research Center, Madison, Wisconsin 53706, USA.
Waterman
P M
PM
Pauza
C D
CD
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D015683:Gene Products, gag / Q000276:immunology*; D007114:Immunization; D008213:Lymphocyte Activation; D008253:Macaca mulatta; D018449:SAIDS Vaccines / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*