Influenza A virus (IAV) poses a constant worldwide threat to human health. Although conventional vaccines are available, their protective efficacy is type or strain specific, and their production is time-consuming. For the control of an influenza pandemic in particular, agents that are immediately effective against a wide range of virus variants should be developed. Although pretreatment of various Toll-like receptor (TLR) ligands have already been reported to be effective in the defense against subsequent IAV infection, the efficacy was limited to specific subtypes, and safety concerns were also raised. In this study, we investigated the protective effect of an attenuated bacterial outer membrane vesicle -harboring modified lipid A moiety of lipopolysaccharide (fmOMV) against IAV infection and the underlying mechanisms. Administration of fmOMV conferred significant protection against a lethal dose of pandemic H1N1, PR8, H5N2, and highly pathogenic H5N1 viruses; this broad antiviral activity was dependent on macrophages but independent of neutrophils. fmOMV induced recruitment and activation of macrophages and elicited type I IFNs. Intriguingly, fmOMV showed a more significant protective effect than other TLR ligands tested in previous reports, without exhibiting any adverse effect. These results show the potential of fmOMV as a prophylactic agent for the defense against influenza virus infection.

中文翻译：

---

细菌外膜囊泡可通过募集和激活巨噬细胞来提供针对流感病毒感染的广谱保护。

甲型流感病毒（IAV）对人类健康构成了持续不断的全球性威胁。尽管可以使用常规疫苗，但是它们的保护功效是类型或毒株特异性的，并且生产耗时。特别是对于控制流感大流行，应开发对多种病毒变种具有立即效力的药物。尽管已经报道了各种Toll样受体（TLR）配体的预处理在抵抗随后的IAV感染方面是有效的，但其功效仅限于特定的亚型，并且也引起了安全隐患。在这项研究中，我们研究了减毒细菌外膜囊泡的脂多糖（fmOMV）的修饰的脂质A部分对IAV感染的保护作用及其潜在机制。fmOMV的使用可对致命剂量的大流行H1N1，PR8，H5N2和高致病性H5N1病毒提供重要保护；这种广泛的抗病毒活性取决于巨噬细胞，但不依赖于中性粒细胞。fmOMV诱导巨噬细胞的募集和激活，并引起I型干扰素。有趣的是，fmOMV显示出比以前的报告中测试的其他TLR配体更显着的保护作用，而没有表现出任何不良作用。这些结果表明，fmOMV作为预防流感病毒感染的预防剂的潜力。fmOMV诱导巨噬细胞的募集和激活，并引起I型干扰素。有趣的是，fmOMV显示出比以前的报告中测试的其他TLR配体更显着的保护作用，而没有表现出任何不良作用。这些结果表明，fmOMV作为预防流感病毒感染的预防剂的潜力。fmOMV诱导巨噬细胞的募集和激活，并引起I型干扰素。有趣的是，fmOMV显示出比以前的报告中测试的其他TLR配体更显着的保护作用，而没有表现出任何不良作用。这些结果表明，fmOMV作为预防流感病毒感染的预防剂的潜力。