Development of adjuvant-combined nasal influenza vaccine

天然流感病毒已显示出在诱导针对A型病毒亚型内的变体的交叉保护方面优于灭活疫苗的上级。自然感染诱导的交叉保护似乎主要是由于呼吸道中交叉反应伊加抗体的诱导。这些事实表明，开发刺激粘膜伊加抗体产生的免疫程序将提高目前灭活疫苗的保护效力。在这方面，已经提倡灭活疫苗的鼻内免疫作为诱导针对流感的分泌型伊加和系统性IgG抗体的手段。然而，单独的灭活疫苗的鼻内免疫不容易产生分泌型伊加抗体。在这种情况下，我们尝试将目前的灭活疫苗与含有0.1%霍乱毒素（CT）的有效佐剂霍乱毒素B亚单位（CT B）一起鼻内接种小鼠。结果表明，鼻内接种疫苗可模拟活病毒对变异病毒攻击的交叉保护作用。此外，我们研究了鼻内免疫的佐剂组合疫苗对人伊加和HI抗体应答的影响。结果表明，与单独的疫苗相比，免疫复合疫苗不仅能显著地诱导人产生分泌型伊加抗体，而且能显著地诱导人产生血清HI抗体。

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.