Impact of hemagglutination activity and M2e immunity on conferring protection against influenza viruses.
Impact of hemagglutination activity and M2e immunity on conferring protection against influenza viruses.
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DOI：
10.1016/j.virol.2022.07.010
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发表时间：
2022-09
期刊：
影响因子：
3.7
通讯作者：
Kang, Sang-Moo
中科院分区：
文献类型：
--
作者：
Oh, Judy;Subbiah, Jeeva;Kim, Ki-Hye;Park, Bo Ryoung;Bhatnagar, Noopur;Garcia, Karla Ruiz;Liu, Rong;Jung, Yu-Jin;Shin, Chong-Hyun;Seong, Baik-Lin;Kang, Sang-Moo
为了提高流感疫苗的交叉保护作用，我们测试了保守的M2e表位与灭活流感病毒（iPR8-M2e*）表面的结合。用化学交联剂处理病毒导致血凝活性降低，不能诱导血凝抑制抗体。尽管诱导了病毒特异性结合IgG抗体，但结合iPR8-M2e*疫苗对同源和异亚型病毒的保护作用较弱。在增强交叉保护的替代方法中，我们开发了一种与甲型流感病毒的M2e和乙型流感病毒的血凝素（HA）梗基因连接的嵌合蛋白（M2e-B茎）疫苗。用灭活的甲型流感病毒补充M2e- b茎接种小鼠，可有效诱导血凝抑制抗体、体液和细胞M2e免疫应答，并增强异亚型保护。本研究证明了HA功能完整性对流感疫苗效力的重要性，并且在流感疫苗中补充M2e-B茎蛋白可能是一种可行的策略，可以提高流感病毒的交叉保护。
To improve cross-protection of influenza vaccination, we tested conjugation of conserved M2e epitopes to the surface of inactivated influenza virus (iPR8-M2e*). Treatment of virus with chemical cross-linker led to diminished hemagglutination activity and failure to induce hemagglutination inhibiting antibodies. Conjugated iPR8-M2e* vaccine was less protective against homologous and heterosubtypic viruses, despite the induction of virus-specific binding IgG antibodies. In alternative approaches to enhance cross-protection, we developed a genetically linked chimeric protein (M2e-B stalk) vaccine with M2e of influenza A and hemagglutinin (HA) stalk of influenza B virus. Vaccination of mice with inactivated influenza A virus supplemented with M2e-B stalk effectively induced hemagglutination inhibiting antibodies, humoral and cellular M2e immune responses, and enhanced heterosubtypic protection. This study demonstrates the importance of HA functional integrity in influenza vaccine efficacy and that supplementation of influenza vaccines with M2e-B stalk protein could be a feasible strategy of improving cross-protection against influenza viruses.
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