Pulmonary surfactant-biomimetic nanoparticles potentiate heterosubtypic influenza immunity
Pulmonary surfactant-biomimetic nanoparticles potentiate heterosubtypic influenza immunity
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DOI：
10.1126/science.aau0810
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发表时间：
2020-02-21
期刊：
影响因子：
56.9
通讯作者：
Wu, Mei X.
中科院分区：
文献类型：
--
作者：
Wang, Ji;Li, Peiyu;Wu, Mei X.
目前的流感疫苗仅提供针对同源病毒的保护。我们合成了肺表面活性物质（PS）-仿生脂质体，其包封干扰素基因诱导剂STING（干扰素基因刺激剂）的激动剂2 '，3'-环鸟苷一磷酸-腺苷一磷酸（cGAMP）。佐剂（PS-GAMP）通过模拟病毒感染的早期阶段而没有伴随的过度炎症，在小鼠中强烈增强流感疫苗诱导的体液和CD 8（+）T细胞免疫应答。鼻内免疫PS-GAMP佐剂H1N1疫苗后两天，对远距离H1N1和H3 N2、H5 N1和H7N9亚型病毒产生了强交叉保护作用，持续至少6个月，同时维持了肺部驻留记忆性CD 8（+）T细胞。然后在雪貂中验证佐剂性。当肺泡上皮细胞（AEC）缺乏斯汀或缝隙连接被阻断，PS-GAMP介导的佐剂在体内基本上被废除。因此，AEC在配置异亚型免疫中起关键作用。
Current influenza vaccines only confer protection against homologous viruses. We synthesized pulmonary surfactant (PS)-biomimetic liposomes encapsulating 2',3'-cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), an agonist of the interferon gene inducer STING (stimulator of interferon genes). The adjuvant (PS-GAMP) vigorously augmented influenza vaccine-induced humoral and CD8(+) T cell immune responses in mice by simulating the early phase of viral infection without concomitant excess inflammation. Two days after intranasal immunization with PS-GAMP-adjuvanted H1N1 vaccine, strong cross-protection was elicited against distant H1N1 and heterosubtypic H3N2, H5N1, and H7N9 viruses for at least 6 months while maintaining lung-resident memory CD8(+) T cells. Adjuvanticity was then validated in ferrets. When alveolar epithelial cells (AECs) lacked Sting or gap junctions were blocked, PS-GAMP-mediated adjuvanticity was substantially abrogated in vivo. Thus, AECs play a pivotal role in configuring heterosubtypic immunity.