Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
J Virol. 2019 May 29;93(12). doi: 10.1128/JVI.00333-19. Print 2019 Jun 15.
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. 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.
乙型流感病毒会引起季节性流行，给公共卫生带来相当大的负担。然而，由于流行株的抗原变化，目前的季节性疫苗的保护效果并不理想。在这项研究中，我们报告了一种基于“嵌合”血凝素的新型通用乙型流感病毒疫苗接种策略。我们通过用来自外来甲型流感血凝素的相应序列替换乙型血凝素的主要抗原位点，生成了嵌合 B 血凝素，并将其表达为可溶性三聚体蛋白。在小鼠模型中，用重组嵌合 B 血凝蛋白进行序贯接种可针对同源和异源乙型流感病毒株提供交叉保护。值得注意的是，我们拯救了表达嵌合 B 血凝素的重组乙型流感病毒，它们可以作为通用乙型流感病毒疫苗的基础。本研究报告了一种基于将抗体反应聚焦于血凝素的保守头部和茎部表位的通用乙型流感病毒疫苗接种策略。已生成重组嵌合流感 B 血凝蛋白和重组病毒作为新型疫苗候选物。该疫苗策略在小鼠模型中提供了广泛的交叉保护。我们的研究结果将为更有效的乙型流感病毒疫苗的开发提供信息和指导。
