Influenza B viruses cause seasonal epidemics and are a considerable burden to public health. However, protection by current seasonal vaccines is suboptimal due to the antigenic changes of the circulating strains. In this study, we report a novel universal influenza B virus vaccination strategy based on "mosaic" hemagglutinins. We generated mosaic B hemagglutinins by replacing the major antigenic sites of the type B hemagglutinin with corresponding sequences from exotic influenza A hemagglutinins and expressed them as soluble trimeric proteins. Sequential vaccination with recombinant mosaic B hemagglutinin proteins conferred cross-protection against both homologous and heterologous influenza B virus strains in the mouse model. Of note, we rescued recombinant influenza B viruses expressing mosaic B hemagglutinins, which could serve as the basis for a universal influenza B virus vaccine.IMPORTANCE This work reports a universal influenza B virus vaccination strategy based on focusing antibody responses to conserved head and stalk epitopes of the hemagglutinin. Recombinant mosaic influenza B hemagglutinin proteins and recombinant viruses have been generated as novel vaccine candidates. This vaccine strategy provided broad cross-protection in the mouse model. Our findings will inform and drive development toward a more effective influenza B virus vaccine.

中文翻译：

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使用“马赛克”血凝素方法开发乙型流感通用疫苗候选人。

乙型流感病毒会导致季节性流行，并给公共健康带来巨大负担。但是，由于循环菌株的抗原变化，当前季节性疫苗的保护作用欠佳。在这项研究中，我们报告了一种基于“马赛克”血凝素的新型通用B型流感病毒疫苗接种策略。我们通过用来自外来的甲型流感血凝素的相应序列替换B型血凝素的主要抗原位点来生成花叶B血凝素，并将它们表达为可溶性三聚体蛋白。重组马赛克B型血凝素蛋白的顺序接种可在小鼠模型中赋予针对同源和异源B型流感病毒株的交叉保护。值得注意的是，我们拯救了表达花叶B血凝素的重组B型流感病毒，重要信息这项工作报告了一种基于针对血凝素保守的头部和茎部表位的抗体应答的通用B型流感病毒疫苗接种策略。已经产生了重组的花叶乙型流感血凝素蛋白和重组病毒作为新的候选疫苗。这种疫苗策略在小鼠模型中提供了广泛的交叉保护。我们的发现将为并推动更有效的乙型流感病毒疫苗的发展提供信息。已经产生了重组的花叶乙型流感血凝素蛋白和重组病毒作为新的候选疫苗。这种疫苗策略在小鼠模型中提供了广泛的交叉保护。我们的发现将为并推动更有效的乙型流感病毒疫苗的发展提供信息。已经产生了重组的花叶乙型流感血凝素蛋白和重组病毒作为新的候选疫苗。这种疫苗策略在小鼠模型中提供了广泛的交叉保护。我们的发现将为并推动更有效的乙型流感病毒疫苗的发展提供信息。