Epigraph hemagglutinin vaccine induces broad cross-reactive immunity against swine H3 influenza virus.
Epigraph hemagglutinin vaccine induces broad cross-reactive immunity against swine H3 influenza virus.
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DOI：
10.1038/s41467-021-21508-6
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发表时间：
2021-02-22
影响因子：
16.6
通讯作者：
Weaver EA
中科院分区：
文献类型：
--
作者：
Bullard BL;Corder BN;DeBeauchamp J;Rubrum A;Korber B;Webby RJ;Weaver EA
猪中的甲型流感病毒感染除了具有人畜共患潜力外，还影响农业。在这里，我们利用epigraph，计算算法，设计一个通用的猪H3流感疫苗。使用5型腺病毒载体递送epigraph血凝素蛋白，并与野生型血凝素和市售灭活疫苗FluSure进行比较。在小鼠中，epigraph疫苗接种导致针对多种swH3分离株的显著交叉反应性抗体和T细胞应答。Epigraph疫苗接种还减少了用三种不同的swH3病毒攻击后小鼠的体重减轻和肺病毒滴度。猪（该疫苗的靶种属）的疫苗接种研究显示，与野生型和FluSure疫苗相比，接种epigraph疫苗后交叉反应性抗体和T细胞应答水平更高。在鼠和猪模型中，epigraph疫苗接种显示出上级的交叉反应性免疫，其应作为通用swH3疫苗进一步研究。在许多动物模型中，一系列流感疫苗与诱导适应性免疫有关。在这里，作者利用计算设计策略并生产猪H3流感疫苗，其在鼠和猪传染病模型中均显示出增强的功效。
Influenza A virus infection in swine impacts the agricultural industry in addition to its zoonotic potential. Here, we utilize epigraph, a computational algorithm, to design a universal swine H3 influenza vaccine. The epigraph hemagglutinin proteins are delivered using an Adenovirus type 5 vector and are compared to a wild type hemagglutinin and the commercial inactivated vaccine, FluSure. In mice, epigraph vaccination leads to significant cross-reactive antibody and T-cell responses against a diverse panel of swH3 isolates. Epigraph vaccination also reduces weight loss and lung viral titers in mice after challenge with three divergent swH3 viruses. Vaccination studies in swine, the target species for this vaccine, show stronger levels of cross-reactive antibodies and T-cell responses after immunization with the epigraph vaccine compared to the wild type and FluSure vaccines. In both murine and swine models, epigraph vaccination shows superior cross-reactive immunity that should be further investigated as a universal swH3 vaccine. A range of Influenza vaccines have been linked to induction of adaptive immunity in a number of animal models. Here, the authors utilize a computational design strategy and produce a swine H3 influenza vaccine which shows enhanced efficacy in both murine and porcine infectious disease models.
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