Double-layered protein nanoparticles induce broad protection against divergent influenza A viruses.
Double-layered protein nanoparticles induce broad protection against divergent influenza A viruses.
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双层蛋白纳米颗粒可引起对逆流感病毒的广泛保护。
DOI：
10.1038/s41467-017-02725-4
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发表时间：
2018-01-24
影响因子：
16.6
通讯作者：
Wang BZ
中科院分区：
文献类型：
--
作者：
Deng L;Mohan T;Chang TZ;Gonzalez GX;Wang Y;Kwon YM;Kang SM;Compans RW;Champion JA;Wang BZ
目前的流感疫苗对甲型流感病毒的保护作用有限。通用流感疫苗将消除季节性流感疫苗的固有局限性。在这里，我们报告的方法，以产生双层蛋白质纳米粒子作为一种通用的流感疫苗。通过将四聚体M2e去溶剂化成蛋白质纳米颗粒核并通过交联无头HA来涂覆这些核来制造层状纳米颗粒。构建并纯化了两个HA系统发育组的代表性无头HA。在小鼠中用所得蛋白质纳米颗粒接种疫苗诱导了强大的持久免疫力，完全保护小鼠免受同一组或两组的不同甲型流感病毒的攻击。结果证明了将结构稳定的HA茎结构域和M2e两者并入通用流感疫苗以提高其保护效力和广度的重要性。这些有效的可分解的蛋白质纳米颗粒在蛋白质药物递送和控制释放方面具有广泛的应用。甲型流感病毒（IAV）蛋白相对保守的结构域是开发通用IAV疫苗的潜在候选者。在此，Deng等联合收割机将两种这样的保守抗原（M2 e和HA茎）组合在双层蛋白纳米颗粒中，并显示其在小鼠中保护对抗趋异IAV。
Current influenza vaccines provide limited protection against circulating influenza A viruses. A universal influenza vaccine will eliminate the intrinsic limitations of the seasonal flu vaccines. Here we report methodology to generate double-layered protein nanoparticles as a universal influenza vaccine. Layered nanoparticles are fabricated by desolvating tetrameric M2e into protein nanoparticle cores and coating these cores by crosslinking headless HAs. Representative headless HAs of two HA phylogenetic groups are constructed and purified. Vaccinations with the resulting protein nanoparticles in mice induces robust long-lasting immunity, fully protecting the mice against challenges by divergent influenza A viruses of the same group or both groups. The results demonstrate the importance of incorporating both structure-stabilized HA stalk domains and M2e into a universal influenza vaccine to improve its protective potency and breadth. These potent disassemblable protein nanoparticles indicate a wide application in protein drug delivery and controlled release. Relatively well conserved domains of influenza A virus (IAV) proteins are potential candidates for the development of a universal IAV vaccine. Here, Deng et al. combine two such conserved antigens (M2e and HA stalk) in a double-layered protein nanoparticle and show that it protects against divergent IAVs in mice.
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影响因子：
158.5
作者：
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影响因子：
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