CHOLERA TOXIN AS AN ADJUVANT FOR GENITAL SIV IMMUNITY

HIV是一种性传播疾病，也是一种疫苗

Significance HIV is a sexually transmitted disease and a vaccine capable of preventing sexual transmission of HIV should elicit mucosal immune responses in the genital tract. Objectives This study should determine if immunization at distant mucosal sites can result in vaginal anti-SIV immune responses and whether the mucosa adjuvant cholera toxin (CT) was useful for this purpose. Results Two rhesus macaques were orally immunized with CT mixed with 1000ug of SIVp55 and 2 animals were orally immunized with CT mixed with 250ug of SIVp55. The animals immunized with CT and high dose antigen made strong systemic immune responses to P55 including antibody, T cell proliferative and T cell cytokine responses to P55. The immune responses in the animal immunized with low dose P55 were weak. Significant levels of anti-p55 IgA antibodies were found in the rectal secretions but not in the vaginal secretions of these animals. Four rhesus macaques were intranasally immunized with CT mixed with SIVp55 and 2 animals were intranasally immunized with 10ug CT mixed with 250ug of SIVp55. The animals immunized with CT made strong systemic immune responses to P55 including antibody, T cell proliferative and T cell cytokine responses to P55. Significant levels of anti-p55 IgA antibodies were found in the rectal secretions and in the vaginal secretions of these animals. This stud y demonstrates that the mucosal adjuvant CT is effective in rhesus macaques. In addition, it is now clear that oral immunization is not an effective method for generating mucosal immune responses in the vagina and that intranasal immunization is an excellent route of immunization for eliciting vaginal immunity. Future Directions Test other vaccine preparations by intranasal route. KEY WORDS mucosal immunity, intranasal immunization, SIV antigens FUNDING NIH Grants AI35545 and RR00169 PUBLICATIONS Kubota, M. C.J. Miller, K. Imaoka, S. Kawabata, K. Fujihashi, J.R. McGhee, H. Kiyono. Oral immunization with simian immunodeficiency virus (SIV) p55 gag and cholera toxin (CT) elicits both mucosal IgA and systemic IgG immune responses in non-human primates. J. Immunol. 158 5321-5329. 1997. Imaoka, K., C.J. Miller, M. Kubota, S. Kawabata, M.B. McChesney, K. Someya, M. Yamamoto, K. Fujihashi, M. Honda, J.R. McGhee, H. Kiyono. Nasal immunization of non-human primates with simian immunodeficiency virus (SIV) p55 gag and cholera toxin (CT) adjuvant induces Th1/Th2 help for virus specific immune responses in reproductive tissues. J. Immunol. 161:5952-5958, 1998. Kawabata, S., C.J. Miller, T. Lehner, K. Fujihashi, M. Kubota, J.R. McGhee, T. Hiroi, H. Kiyono. Induction of Th2 cytokine expression for p27-specific IgA B cell responses after TLN immunization with SIV antigens in rhesus macaques. J. Infect. Dis. 177:26-33, 1998.