Development of adjuvant-combined nasal influenza vaccine

佐剂联合鼻流感疫苗的研制

基本信息

批准号：
04557026
负责人：
TAMURA Shinichi
金额：
$ 12.61万
依托单位：
National Institute of Health, Dept.of Pathology
依托单位国家：
日本
项目类别：
Grant-in-Aid for Developmental Scientific Research (B)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1994
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-04557026/
关键词：
influenza intranasal vaccination inactivated vaccine adjuvant heat-labile toxin IgA 交差感染阻止

项目摘要

Natural influenza virus has been shown to be superior to the inactivated vaccine for inducing cross-protection against variants within a subtype of A type virus. The cross-protection induced by natural infection seems to be largely due to the induction of cross-reacting IgA antibodies in the respiratory tract. These facts suggest that the development of immunization procedure to stimulate mucosal IgA antibody production would improve the protective efficacy of the current inactivated vaccine. In this regard, intranasal immunization of inactivated vaccine has been advocated as means of inducing secretory IgA and systemic IgG antibodies against influenza. However, the intranasal immunization of inactivated vaccine alone cannot easily generate the secretory IgA antibodies. Under these circumstances, we attempted to inoculate intranasally the current inactivated vaccine together with a potent adjuvant, cholera toxin B subunit (CTB) containing 0.1% of CT,in mice. The results demonstrated that the nasal administration of the adjuvant-combined vaccine into mice can mimic the efficacy of live virus in inducing cross-protection against variant virus challenge. Moreover, we examined the effect of the intranasal immunization of the adjuvant-combined vaccine on IgA and HI antibody responses in humans. The results demonstrated that the adjuvant-combined vaccine can elicit significantly not only secretory IgA antibody but also serum HI antibody, as compared with vaccine alone, in humans.

天然流感病毒已被证明优于灭活疫苗，可诱导针对 A 型病毒亚型内变异的交叉保护。自然感染引起的交叉保护似乎主要是由于呼吸道中交叉反应 IgA 抗体的诱导。这些事实表明，开发刺激粘膜IgA抗体产生的免疫程序将提高当前灭活疫苗的保护功效。在这方面，提倡使用灭活疫苗鼻内免疫作为诱导针对流感的分泌性IgA和全身性IgG抗体的手段。然而，单独使用灭活疫苗进行鼻内免疫并不能轻易产生分泌型IgA抗体。在这种情况下，我们尝试将目前的灭活疫苗与含有0.1% CT的强效佐剂霍乱毒素B亚基（CTB）一起鼻内接种给小鼠。结果表明，对小鼠鼻腔施用佐剂组合疫苗可以模拟活病毒诱导针对变异病毒攻击的交叉保护的功效。此外，我们还研究了佐剂组合疫苗鼻内免疫对人类 IgA 和 HI 抗体反应的影响。结果表明，与单独的疫苗相比，佐剂组合疫苗不仅可以在人体中显着诱导分泌型 IgA 抗体，而且还可以显着诱导血清 HI 抗体。