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一种通用流感纳米疫苗可使“混合宿主”获得潜在阻断跨物种传播的能力。

A Universal Influenza Nanovaccine for "Mixing Vessel" Hosts Confers Potential Ability to Block Cross-Species Transmission.

机构信息

Henan Provincial Key Laboratory of Animal Immunology, Henan Academy of Agricultural Sciences, Zhengzhou, 450002, China.

College of Veterinary Medicine, Northwest A&F University, Yangling, 712100, China.

出版信息

Adv Healthc Mater. 2019 Aug;8(16):e1900456. doi: 10.1002/adhm.201900456. Epub 2019 Jul 3.

Abstract

Influenza A virus (IAV), a deadly zoonotic pathogen, poses a tremendous threat and burden to global health systems. Pigs act as "mixing vessel" hosts to support and generate new pandemic viruses. Preventing the spread of IAV in pigs effectively can delay or even block cross-species transmission. Universal vaccines based on the highly conserved ectodomain of influenza matrix protein 2 (M2e) have been widely reported, but have not been applied due to inadequate protection. Porcine circovirus type 2 (PCV2) causes immunosuppression and promotes swine influenza virus (SIV) infection. Here, M2e is inserted into capsid protein of PCV2 without burying the neutralizing epitopes and self-assembles to form a bivalent nanovaccine. Inoculation with the nanovaccine induces robust M2e- and PCV2-specific immune responses. The nanovaccine confers protection against lethal challenges of IAV from different species in mice, and significantly reduces SIV titers in pigs' respiratory tract and blocks SIV transmission. These results indicate that the nanovaccine is an economical and promising PCV2 and universal IAV bivalent vaccine, and it will synergistically and powerfully offer potential ability to block IAV cross-species reassortment and transmission.

摘要

甲型流感病毒(IAV)是一种致命的人畜共患病原体,对全球卫生系统构成了巨大威胁和负担。猪作为“混合容器”宿主,支持并产生新的大流行病毒。有效防止 IAV 在猪中的传播可以延迟甚至阻断跨物种传播。基于流感基质蛋白 2(M2e)高度保守的外域的通用疫苗已被广泛报道,但由于保护不足尚未应用。猪圆环病毒 2 型(PCV2)引起免疫抑制并促进猪流感病毒(SIV)感染。在这里,M2e 被插入到 PCV2 的衣壳蛋白中,而不掩埋中和表位,并自我组装形成二价纳米疫苗。接种纳米疫苗可诱导强烈的 M2e 和 PCV2 特异性免疫反应。该纳米疫苗可保护小鼠免受来自不同物种的 IAV 的致死性挑战,并显著降低猪呼吸道中的 SIV 滴度并阻断 SIV 传播。这些结果表明,该纳米疫苗是一种经济且有前途的 PCV2 和通用 IAV 二价疫苗,它将协同且有力地提供潜在能力来阻断 IAV 的跨物种重配和传播。

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