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.
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We thank M. Busch, Keith Reimann, and Nancy Miller for helpful discussion, the Primate Services Unit at the CNPRC Lili Guo, and Roxana Colon for excellent technical assistance. We also thank Dr Roederer, National Institutes of Health Vaccine Research Center, for providing the SPICE and PESTLE software, and Dr Watkins, University of Wisconsin, for providing the MHC peptide tetramers complexes. This work was supported by Public Health Services grants U51RR00169, from the National Center for Research Resources; and P01 AI066314 and R01 AI44480 from the National Institute of Allergy and Infectious Diseases and a gift from the James B Pendleton Charitable Trust.