Enhancing the cross protective efficacy of live attenuated influenza virus vaccine by supplemented vaccination with M2 ectodomain virus-like particles
Enhancing the cross protective efficacy of live attenuated influenza virus vaccine by supplemented vaccination with M2 ectodomain virus-like particles
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DOI：
10.1016/j.virol.2019.01.017
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发表时间：
2019-03-01
期刊：
影响因子：
3.7
通讯作者：
Kang, Sang-Moo
中科院分区：
文献类型：
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作者：
Lee, Young-Tae;Kim, Ki-Hye;Kang, Sang-Moo
目前的流感疫苗，包括减毒活流感病毒（LAIV）提供了针对漂移和潜在的大流行毒株的次优保护。我们假设用高度保守的抗原靶标M2胞外域（M2 e）补充LAIV将通过诱导对保守抗原靶标的体液和细胞免疫应答来赋予交叉保护。鼻内接种LAIV（A/Netherlands/602/09，H1N1）并补充含有病毒样颗粒的串联重复序列M2 e（M2 e5 x VLP）可诱导产生M2 e和病毒特异性抗体。在异亚型病毒攻击后，小鼠的M2 e5 x VLP补充的LAIV疫苗接种通过防止体重减轻和降低肺病毒滴度诱导显著改善的交叉保护。对异亚型免疫的进一步机制研究表明，对M2 e和核蛋白的T细胞应答以及对M2 e和病毒的全身和粘膜抗体可能有助于交叉保护。因此，本研究证明了一种新的疫苗接种策略，通过补充保守的M2 e抗原靶标来提高LAIV的交叉保护效力。
Current influenza vaccines including live attenuated influenza virus (LAIV) provide suboptimal protection against drift and potential pandemic strains. We hypothesized that supplementing LAIV with a highly conserved antigenic target M2 ectodomain (M2e) would confer cross-protection by inducing humoral and cellular immune responses to conserved antigenic targets. Intranasal vaccination with LAIV (A/Netherlands/602/09, H1N1) supplemented with tandem repeat M2e containing virus-like particles (M2e5x VLP) induced M2e- and virus-specific antibodies. Upon heterosubtypic virus challenge, M2e5x VLP-supplemented LAIV vaccination of mice induced significantly improved cross protection by preventing weight loss and lowering lung viral titers. Further mechanistic studies on heterosubtypic immunity suggest that T cell responses to M2e and nucleoprotein as well as systemic and mucosal antibodies to M2e and viruses might be contributing to cross protection. Therefore, this study demonstrates a novel vaccination strategy to improve the cross protective efficacy of LAIV by supplementing with a conserved M2e antigenic target.