studies on the mechanism by which nasal influenza vaccine enhances the efficacy of protection

我们在前期的研究中发现，流感灭活疫苗与霍乱毒素B亚单位（CT B）联合鼻内接种小鼠，在诱导呼吸道产生交叉反应性伊加抗体的同时，也能对变异病毒感染产生交叉保护作用。灭活疫苗含有流感病毒的七种蛋白组分。其中，表面糖蛋白，血凝素（HA），其在相同亚型内略有不同，在相同类型内变化很大，已知是参与诱导保护性抗体的主要蛋白质。此外，核心蛋白，核蛋白（NP），这是交叉反应，在相同的类型，是已知的另一个主要组成部分参与从流感的恢复。本研究旨在阐明HA和NP在CTB鼻内免疫小鼠抗流感防御机制中的作用。这将导致开发有效的鼻流感组分疫苗。结果表明，PR8 HA分子与CTB一起鼻内接种到小鼠中不仅赋予针对同源病毒感染的保护，而且赋予针对异源病毒感染的保护。CTB结合的HA分子免疫小鼠后，其呼吸道抗HA伊加Ab被动进入呼吸道，直接介导交叉保护作用。因此，HA是阻断经鼻接种的小鼠中的感染的基本疫苗组分之一。另一方面，鼻内接种PR8 NP分子与CTB诱导的记忆细胞参与加速诱导CTL应答。此外，CTL在呼吸道中加速清除病毒感染的细胞，导致促进从流感中恢复。因此，在缺乏局部Ab的情况下，NP似乎也是有用的疫苗组分。

In our previous studies, We demonstrated that intranasal inoculation of influenza inactivated vaccine together with cholera toxin B subunit(CTB)into mice can provide cross-protection against variant virus infection in parallel with the induction of cross-reacting IgA antibodies (Ab) in the respiratory tract. The inactivated vaccine contained seven protein components of influenza virus. Among them, surface glycoprotein, hemagglutinin(HA), which varies slightly within the same subtype and largely within the same type, is known to be a major protein involved in the induction of protective antibodies. In addition, core protein, nucleoprotein(NP), which is cross-reactive in the same type, is known to be another major component involved in the recovery from influenza. The present study was designed to elucidate the role of HA and NP in the defense mechanism against influenza in the mice immunized intranasally together with CTB. This would lead to the development of the effective nasal influenza component vaccine. The results show that intranasal inoculation of PR8 HA molecules together with CTB into mice conferred protection against not only homologous virus infection but also heterologous virus infection. Moreover, the respiratory tract anti-HA IgA Ab from mice immunized with CTB-combined HA molecules mediated directly the cross-protection when transferred passively into the respiratory tract. Thus,the HA is one of the essential vaccine components in the blockade of infection in the nasally-vaccinated mice. On the other hand, intranasal inoculation of PR8 NP molecules together with CTB induced memory cells involved in the accelerated induction of CTL responses. Moreover, the accelerated elimination of virus-infected cells by CTL in the respiratory tract resulted in the facilitation of the recovery from influenza. Consequently, the NP seems to be also a useful vaccine component under the absence of local Ab.