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 能够防止性传播艾滋病毒的人应该引起粘膜 生殖道中的免疫反应。目标：这项研究应该 确定在较远的粘膜部位接种疫苗是否会导致 阴道抗SIV免疫反应与黏膜佐剂的关系 霍乱毒素(CT)对此很有用。结果2只恒河猴 用沙眼衣原体与1000ug SIVp55混合口服免疫猕猴。 2只动物口服CT和250微克的SIVp55。 用沙眼衣原体和大剂量抗原免疫的动物变得强壮 对P55的系统免疫反应，包括抗体、T细胞 增殖和T细胞因子对P55的反应。免疫者 小剂量P55免疫动物的反应较弱。 在直肠中发现了显著水平的抗P55 IgA抗体 这些动物的阴道分泌物中没有分泌物。四 沙眼衣原体与SIVp55混合免疫恒河猴 2只动物鼻腔免疫10ug CT与 250微克SIVP55。用沙眼衣原体免疫的动物表现出较强的系统性 P55的免疫应答包括抗体、T细胞增殖和T细胞 细胞细胞因子对p55的反应。抗P55 IgA抗体水平显著升高 在直肠分泌物和阴道中发现了抗体。 这些动物的分泌物。这项研究表明， 粘膜佐剂CT对恒河猴有效。此外，它还 现在很清楚，口服免疫不是一种有效的治疗方法 在阴道和鼻腔内产生粘膜免疫反应 免疫是一种很好的免疫途径 阴道免疫力。未来方向测试其他疫苗制剂 通过鼻腔途径。关键词黏膜免疫，鼻腔 免疫、SIV抗原资助NIH资助AI35545和RR00169 出版物：Kubota，M.C.J.Miller，K.Imaoka，S.Kawabata，K. 首页--期刊主要分类--期刊细介绍--期刊题录与文摘--期刊细介绍猿猴口服免疫 免疫缺陷病毒P55 Gag和霍乱毒素(CT)诱导 非人黏膜免疫球蛋白A和系统免疫球蛋白免疫应答的研究 灵长类动物。J.免疫。158 5321-5329。1997年。Imaoka，K.，C.J. 首页--期刊主要分类--期刊细介绍--期刊题录与文摘--期刊详细文摘内容 首页--期刊主要分类--期刊细介绍--期刊题录与文摘--期刊详细文摘内容鼻腔 猴免疫缺陷病毒对非人灵长类动物的免疫 (SIV)P55 Gag和霍乱毒素(CT)佐剂诱导Th1/Th2辅助治疗 生殖组织中的病毒特异性免疫反应。J.免疫。 161：5952-5958,1998。首页--期刊主要分类--期刊细介绍--期刊题录与文摘--期刊详细文摘内容 首页--期刊主要分类--期刊细介绍--期刊题录与文摘--期刊详细文摘内容诱导 Th2细胞因子表达对p27特异性IgA B细胞免疫应答的影响 SIV抗原免疫恒河猴TLN的研究J.感染。 迪什。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.