1. ¹Center for Comparative Medicine, University of California, Davis, California, USA
2. ²California National Primate Research Center, University of California, Davis, California, USA
3. ³Department of Veterinary and Biomedical Sciences, University of Minnesota, St Paul, Minnesota, USA
4. ⁴Department of Microbiology, University of Minnesota, St Paul, Minnesota, USA
5. ⁵Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis, California, USA
6. ⁶Division of Infectious Diseases, School of Medicine, University of California, Davis, California, USA

Correspondence: CJ Miller, (cjmiller@ucdavis.edu)

Received 16 January 2008; Accepted 28 January 2008; Published online 5 March 2008.

Abstract

Live attenuated lentivirus immunization is the only vaccine strategy that elicits consistent protection against intravaginal challenge with pathogenic simian immunodeficiency virus (SIV). To determine the mechanism of protection in rhesus monkeys infected with attenuated simian–human immunodeficiency virus (SHIV)89.6, a detailed analysis of SIV Gag-specific T-cell responses in several tissues including the genital tract was performed. Six months after SHIV infection, antiviral T-cell responses were rare in the cervix; however, polyfunctional, cytokine-secreting, and degranulating SIV Gag-specific CD4⁺ T cells were consistently found in the vagina of the immunized macaques. SIV-specific CD8⁺ T cells were also detected in the vagina, blood, and genital lymph nodes of most of the animals. Thus, an attenuated SHIV vaccine induces persistent antiviral T cells in tissues, including the vagina, where these effector T-cell responses may mediate the consistent protection from vaginal SIV challenge observed in this model.