Generation of a Live Attenuated Influenza Vaccine that Elicits Broad Protection in Mice and Ferrets
Generation of a Live Attenuated Influenza Vaccine that Elicits Broad Protection in Mice and Ferrets
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产生对小鼠和雪貂产生广泛保护的减毒流感活疫苗
DOI：
10.1016/j.chom.2017.02.007
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发表时间：
2017-03-08
影响因子：
30.3
通讯作者：
Cheng，Genhong
中科院分区：
文献类型：
--
作者：
Wang，Lulan;Liu，Su-Yang;Cheng，Genhong
迫切需要能够提供有效和广泛保护的新型流感疫苗。减毒活病毒是有吸引力的候选疫苗，因为它们既能引起体液免疫反应，又能引起细胞免疫反应。然而，最近的减毒活流感疫苗(LAIV)配方并没有起到保护作用。我们结合了流感病毒的高覆盖率转座子突变和快速高通量减毒筛选，产生了W7-791，一种活的减毒突变病毒株。W7-791在成年和新生小鼠中只产生一过性无症状感染，即使在剂量比亲本菌株的LD50高100倍时也是如此。单次注射W7-791可以完全保护小鼠免受H1N1、H3N2和H5N1毒株的致命攻击，并改善雪貂的病毒清除。过继转移来自W7-791免疫小鼠的T细胞提供了异种保护，表明T细胞介导的免疫作用。这些研究提出了一种LAIV开发战略，以快速生成和筛选整个病毒克隆文库。
New influenza vaccines that provide effective and broad protection are desperately needed. Live attenuated viruses are attractive vaccine candidates because they can elicit both humoral and cellular immune responses. However, recent formulations of live attenuated influenza vaccines (LAIVs) have not been protective. We combined high-coverage transposon mutagenesis of influenza virus with a rapid high-throughput screening for attenuation to generate W7-791, a live attenuated mutant virus strain. W7-791 produced only a transient asymptomatic infection in adult and neonatal mice even at doses 100-fold higher than the LD50of the parent strain. A single administration of W7-791 conferred full protection to mice against lethal challenge with H1N1, H3N2, and H5N1 strains, and improved viral clearance in ferrets. Adoptive transfer of T cells from W7-791-immunized mice conferred heterologous protection, indicating a role for T cell-mediated immunity. These studies present an LAIV development strategy to rapidly generate and screen entire libraries of viral clones.