Influenza H1 Mosaic Hemagglutinin Vaccine Induces Broad Immunity and Protection in Mice
Influenza H1 Mosaic Hemagglutinin Vaccine Induces Broad Immunity and Protection in Mice
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DOI：
10.3390/vaccines7040195
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发表时间：
2019-12-01
期刊：
影响因子：
7.8
通讯作者：
Weaver, Eric A.
中科院分区：
文献类型：
--
作者：
Corder, Brigette N.;Bullard, Brianna L.;Weaver, Eric A.
每年，全球约有5-10%的成人和20-30%的儿童感染甲型流感病毒（IAV）。预防感染的主要方法是接种疫苗。然而，疫苗接种仅诱导菌株特异性和瞬时免疫。需要诱导针对广泛多样性的IAV的交叉保护性免疫的疫苗策略。在这里，我们开发并测试了一种新的嵌合H1 HA免疫原。嵌合免疫原在计算机上优化，以包括最有潜力的B和T细胞表位（PBTE）的人H1 IAV的不同群体。系统发育分析表明，镶嵌HA定位于非大流行的2009年株，其中包括最广泛的多样性在H1 IAV人口。我们将嵌合H1免疫原与野生型HA免疫原和商业灭活流感疫苗Fluzone进行了比较。当通过ELISA分析时，嵌合免疫原诱导针对所有四种不同H1 HA蛋白的更强的抗体应答。当分析T细胞应答时，嵌合免疫原再次诱导针对所有4种不同HA菌株的更强的细胞免疫。马赛克免疫小鼠中不仅T细胞反应的强度最强，而且识别的表位数量也更大。嵌合免疫小鼠对三种不同的IAV毒株的攻击表现出较强的交叉保护作用。这些数据表明，嵌合免疫原诱导强的交叉保护性免疫，并应进一步研究作为一种通用的流感疫苗。
Annually, influenza A virus (IAV) infects similar to 5-10% of adults and 20-30% of children worldwide. The primary resource to protect against infection is by vaccination. However, vaccination only induces strain-specific and transient immunity. Vaccine strategies that induce cross-protective immunity against the broad diversity of IAV are needed. Here we developed and tested a novel mosaic H1 HA immunogen. The mosaic immunogen was optimized in silico to include the most potential B and T cell epitopes (PBTE) across a diverse population of human H1 IAV. Phylogenetic analysis showed that the mosaic HA localizes towards the non-pandemic 2009 strains which encompasses the broadest diversity in the H1 IAV population. We compared the mosaic H1 immunogen to wild-type HA immunogens and the commercial inactivated influenza vaccine, Fluzone. When analyzed by ELISA, the mosaic immunogen induced stronger antibody responses against all four diverse H1 HA proteins. When analyzing T cell responses, again the mosaic immunogen induced stronger cellular immunity against all 4 diverse HA strains. Not only was the magnitude of T cell responses strongest in mosaic immunized mice, the number of epitopes recognized was also greater. The mosaic vaccinated mice showed strong cross-protection against challenges with three divergent IAV strains. These data show that the mosaic immunogen induces strong cross-protective immunity and should be investigated further as a universal influenza vaccine.