Induction of influenza type A virus-specific resistance by immunization of mice with a synthetic multiple antigenic peptide vaccine that contains ectodomains of matrix protein 2

Induction of influenza type A virus-specific resistance by immunization of mice with a synthetic multiple antigenic peptide vaccine that contains ectodomains of matrix protein 2
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DOI:
10.1016/s0264-410x(03)00040-9
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发表时间:
2003-06-02
期刊:
影响因子:
5.5
通讯作者:
Gerhard, W
Gerhard, W
中科院分区:
医学3区
文献类型:
--
作者:
Mozdzanowska, K;Feng, JQ;Gerhard, W

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基质蛋白2 (M2)是甲型流感病毒的跨膜蛋白。它包含一个23 aa长的外结构域(M2e),在人类甲型流感病毒中高度保守。已证明m2e特异性抗体在体外和体内限制病毒生长,因此有可能对甲型流感病毒感染提供交叉反应性抗性。我们尝试用含有共价连接的M2e和th决定肽的合成多抗原肽(MAP)构建物诱导M2e特异性保护。经鼻内注射两次M2e-MAPs佐剂的小鼠在呼吸道的所有部位表现出对病毒复制的显著抗性。与连续两次异亚型感染的小鼠相比,鼻腔和气管组织的抗性强度相似,但肺组织的抗性较低。重要的是,M2e-MAP和感染免疫小鼠的保护作用似乎是由不同的免疫机制介导的。这表明,通过结合这两种保护活动,可以实现更强的保护。2003爱思唯尔科学有限公司版权所有。
Matix protein 2 (M2) is a transmembrane protein of influenza type A virus. It contains a 23 aa long ectodomain (M2e) that is highly conserved amongst human influenza type A viruses. M2e-specific antibodies have been shown to restrict virus growth in vitro and in vivo and thus have the potential of providing cross-reactive resistance to influenza type A virus infection. We attempted to induce M2e-specific protection with synthetic multiple antigen peptide (MAP) constructs that contained covalently linked M2e- and Th-determinant peptides. Mice, vaccinated twice by the intranasal (i.n.) route with adjuvanted M2e-MAPs exhibited significant resistance to virus replication in all sites of the respiratory tract. Compared to mice primed by two consecutive heterosubtypic infections, resistance was of similar strength in nasal and tracheal tissue but lower in pulmonary tissue. Importantly, the protection in M2e-MAP- and infection-immunized mice appeared to be mediated by distinct immune mechanisms. This suggests that stronger protection may be achievable by combining both protective activities. (C) 2003 Elsevier Science Ltd. All rights reserved.