CHOLERA TOXIN AS AN ADJUVANT FOR GENITAL SIV IMMUNITY

意义艾滋病毒是一种性传播疾病和疫苗 能够防止艾滋病毒的性传播，应引起粘膜 生殖道的免疫反应。 目的本研究应 确定远处粘膜部位的免疫接种是否会导致 阴道抗SIV免疫反应和粘膜佐剂是否 霍乱毒素（CT）可用于此目的。 结果2只恒河猴 用与1000 μ g SIVp 55混合的CT口服免疫猕猴， 2只动物用与250 μ g SIVp 55混合的CT口服免疫。 CT和高剂量抗原免疫动物， 针对P55的系统性免疫应答，包括抗体、T细胞 增殖和T细胞细胞因子对P55的应答。 免疫 用低剂量P55免疫的动物中的应答较弱。 直肠癌组织中抗p55伊加抗体水平显著升高， 但这些动物的阴道分泌物中没有。 四 用CT与SIVp 55混合物鼻内免疫恒河猴 2只动物鼻内免疫10 μ g CT， 250 μ g SIVp55。 CT免疫动物， 针对P55的免疫应答包括抗体、T细胞增殖和T 细胞因子对P55的反应。 显著水平的抗p55伊加 在直肠分泌物和阴道分泌物中发现了抗体 这些动物的分泌物。 这项研究表明， 粘膜辅助CT在恒河猴中有效。 此外还 现在很清楚，口服免疫不是一种有效的方法， 在阴道内产生粘膜免疫反应， 免疫是一种很好的免疫途径， 阴道免疫 未来方向测试其他疫苗制剂 通过鼻内途径。 关键词粘膜免疫，鼻内 免疫、SIV抗原资助NIH赠款AI 35545和RR 00169 Kubota，M. C. J.米勒，K.今冈湾Kawabata，K. Fujihashi，J.R. McGhee，H.清野 猴口服免疫 免疫缺陷病毒（SIV）p55 gag和霍乱毒素（CT）抗体 非人类的粘膜伊加和全身IgG免疫应答 灵长类动物 J. Immunol.1585321 -5329. 1997. Imaoka，K.，C.J. 米勒，M. Kubota，S. Kawabata，M.B. McChesney，K. Someya，M. 山本K. Fujihashi，M.本田McGhee，H.清野 鼻 用猴免疫缺陷病毒免疫非人灵长类动物 (SIV)p55 gag和霍乱毒素（CT）佐剂诱导Th 1/Th 2， 生殖组织中的病毒特异性免疫应答。 J. Immunol. 161：5952-5958，1998. Kawabata，S.，C. J.米勒，T. Lehner，K. Fujihashi，M.久保田McGhee，T. Hiroi，H.清野 诱导 Th 2细胞因子表达的p27特异性伊加B细胞反应 恒河猴中SIV抗原的TLN免疫。 J. Infect. Dis. 177：26-33，1998.

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.