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Nasal Immunization of Nonhuman Primates with Simian Immunodeficiency Virus p55^gag and Cholera Toxin Adjuvant Induces Th1/Th2 Help for Virus-Specific Immune Responses in Reproductive Tissues¹

Koichi Imaoka^*,, Christopher J. Miller, Mitsuru Kubota^*, Michael B. McChesney, Barbara Lohman, Masafumi Yamamoto^*,¶, Kohtaro Fujihashi^*, Kenji Someya^§, Mitsuo Honda^§, Jerry R. McGhee^* and Hiroshi Kiyono^2,*,¶

^* Immunobiology Vaccine Center and Departments of Oral Biology and Microbiology, University of Alabama, Birmingham, AL 35294; Department of Microbiology, National Institute of Public Health, Minato, Tokyo, Japan; California Regional Primate Research Center, University of California, Davis, CA 95615; ^§ AIDS Research Center, National Institute of Infectious Diseases, Shinjuku, Tokyo, Japan; and ^¶ Department of Mucosal Immunology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan

Female rhesus macaques were nasally immunized with p55^gag (p55) of SIV and cholera toxin as a mucosal adjuvant. Nasal immunization induced Ag-specific IgA and IgG Abs in mucosal secretions (e.g., cervicovaginal secretions, rectal washes, and saliva) and serum. Furthermore, high numbers of p55-specific IgA and IgG Ab-forming cells were induced in mucosal effector sites, i.e., uterine cervix, intestinal lamina propria, and nasal passage. p55-specific CD4⁺ T cells in both systemic and mucosal compartments expressed IFN- and IL-2 (Th1-type)- as well as IL-5, IL-6, and IL-10 (Th2-type)-specific mRNA. Moreover, p55-specific CTL activity was demonstrated in lymphocytes from blood, tonsils, and other lymphoid tissues. These results show that nasal immunization with SIV p55 with cholera toxin elicits both Th1- and selective Th2-type cytokine responses associated with the induction of SIV-specific mucosal and serum Abs, and CTL activity. These results offer a promise for the development of protective mucosal immunity to SIV.

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