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

鼻流感疫苗增强防护功效的机制研究

• 批准号: 03670241
• 负责人: TAMURA Shin-ichi
• 金额: $ 1.34万
• 依托单位: National Institute of Health
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03670241/
• 关键词: influenza vaccine; cholera toxin B subunit; hemagglutinin; uncleoprotein; CTL; nasal vaccination; 経鼻接種ワクチン; インフルエンザワクチン; 感染からの回復; 経鼻接種; 上気道感染; 下気道感染

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.

在我们以前的研究中，我们证明了流感灭活疫苗与霍乱毒素B亚单位(CTB)联合鼻腔接种小鼠，可以在诱导呼吸道交叉反应的IgA抗体(Ab)的同时，对变异病毒感染提供交叉保护。灭活疫苗含有流感病毒的七种蛋白质成分。其中，血凝素(HA)是一种主要参与保护性抗体诱导的蛋白质，它在同一亚型中略有不同，在同一亚型中有很大差异。此外，核心蛋白，即核蛋白(NP)，在同一类型中具有交叉反应，已知是流感康复过程中的另一个主要成分。本研究旨在阐明HA和NP在CTB鼻腔免疫小鼠对抗流感的防御机制中的作用。这将导致有效的鼻流感成分疫苗的开发。结果表明，PR8HA分子与CTB联合鼻腔接种小鼠，不仅对同源病毒感染有保护作用，而且对异源病毒感染也有保护作用。CTB结合HA分子免疫的小鼠呼吸道抗HA IgA抗体被动进入呼吸道后可直接介导交叉保护作用。因此，HA是阻断鼻腔接种小鼠感染的重要疫苗成分之一。另一方面，鼻腔接种PR8NP分子与CTB一起诱导记忆细胞参与CTL反应的加速诱导。此外，CTL加速清除呼吸道中的病毒感染细胞，有助于流感的康复。因此，在缺乏局部抗体的情况下，NP似乎也是一种有用的疫苗成分。

项目成果

Hirabayashi,Y., et al.: "H-2-unrestricted adjuvant effect of cholera toxin B subunit on murine antibody responses to influenza virus hemagglutinin" Immunology. 72. 329-335 (1991)

Hirabayashi,Y., et al.：“霍乱毒素 B 亚基对小鼠抗体对流感病毒血凝素反应的 H-2-无限制佐剂作用”免疫学。

TAMURA,S.-I.,et al.: "Cross-protection against influenza A virus infection by passively transferred respiratory tract IgA antibodies to different hemagglutinin molecules." Eur.J.Immunol.21. 1337-1344 (1991)

TAMURA,S.-I.,et al.：“通过被动转移呼吸道 IgA 抗体至不同的血凝素分子来交叉保护甲型流感病毒感染。”

Tamura,S.-I.,et al.: "Cross-protection against influenza A virus infection by passively transferred respiratory tract IgA antibodies to different hemagglutinin molecules" Eur.J.Immunol.21. 1337-1344 (1991)

Tamura,S.-I.,et al.：“通过被动地将呼吸道 IgA 抗体转移到不同的血凝素分子来对抗甲型流感病毒感染的交叉保护”Eur.J.Immunol.21。