Induction of heterosubtypic immunity to influenza A virus using a DNA vaccine expressing hemagglutinin-C3d fusion proteins.
Induction of heterosubtypic immunity to influenza A virus using a DNA vaccine expressing hemagglutinin-C3d fusion proteins.
复制标题
使用表达血凝素-C3d 融合蛋白的 DNA 疫苗诱导针对甲型流感病毒的异亚型免疫。
DOI：
10.1016/s0264-410x(02)00539-x
复制
发表时间：
2003
期刊：
影响因子：
5.5
通讯作者：
Ross,TedM
中科院分区：
文献类型：
--
作者：
Mitchell,JudyA;Green,ThomasD;Bright,RickA;Ross,TedM
甲型流感病毒不同亚型之间的交叉保护作用归因于异亚型免疫（HSI）。尽管HSI可以在不存在抗HA或抗NA抗体的情况下发生，但HSI似乎部分由交叉反应性抗体介导。在这项研究中，我们研究了表达流感HA融合三个拷贝的小鼠补体C3 d（HA-mC 3d 3）的DNA疫苗的效果。HA-mC 3d 3比非融合形式的HA更有效地引发异亚型免疫，并保护小鼠免受不同亚型流感的致死性攻击。从两种流感病毒株A/波多黎各/8/34（H1N1）或A/Aichi/2/68-x31（H3 N2）构建编码各种形式HA的质粒。分析接种小鼠的抗HA滴度增强、抗体亲和力成熟、血凝素抑制活性和细胞因子谱改变。HA-mC 3d 3-DNA疫苗接种的小鼠受到保护免于异源流感攻击，即使来自这些小鼠的血清对异源病毒没有病毒中和活性。
Cross-protection between different subtypes of influenza A virus has been attributed to heterosubtypic immunity (HSI). Although, HSI can occur in the absence of anti-HA or anti-NA antibodies, HSI seems to be mediated, in part, by cross-reactive antibodies. In this study, we examined the effects of a DNA vaccine expressing an influenza HA fused to three copies of murine C3d of complement (HA–mC3d3). HA–mC3d3elicited heterosubtypic immunity more efficiently than non-fused forms of HA and protected mice from lethal challenge of influenza with different subtypes. Plasmid encoding for various forms of HA were constructed from two influenza strains, A/Puerto Rico/8/34 (H1N1) or A/Aichi/2/68-x31 (H3N2). Vaccinated mice were analyzed for enhancement of anti-HA titers, affinity maturation of antibody, hemagglutinin-inhibition activity, and altered cytokine profiles. The HA–mC3d3–DNA vaccinated mice were protected from heterologous influenza challenge, even though sera from these mice had no viral-neutralizing activity against heterologous virus.