Seasonal influenza vaccines offer little protection against pandemic influenza virus strains. It is difficult to create effective prepandemic vaccines because it is uncertain which influenza virus subtype will cause the next pandemic. In this work, we developed a nucleoside-modified messenger RNA (mRNA)–lipid nanoparticle vaccine encoding hemagglutinin antigens from all 20 known influenza A virus subtypes and influenza B virus lineages. This multivalent vaccine elicited high levels of cross-reactive and subtype-specific antibodies in mice and ferrets that reacted to all 20 encoded antigens. Vaccination protected mice and ferrets challenged with matched and mismatched viral strains, and this protection was at least partially dependent on antibodies. Our studies indicate that mRNA vaccines can provide protection against antigenically variable viruses by simultaneously inducing antibodies against multiple antigens.

中文翻译：

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针对所有已知流感病毒亚型的多价核苷修饰 mRNA 疫苗

季节性流感疫苗对大流行性流感病毒株几乎没有保护作用。由于不确定哪种流感病毒亚型将导致下一次大流行，因此很难研制出有效的大流行前疫苗。在这项工作中，我们开发了一种核苷修饰的信使 RNA (mRNA)-脂质纳米颗粒疫苗，编码来自所有 20 种已知甲型流感病毒亚型和乙型流感病毒谱系的血凝素抗原。这种多价疫苗在小鼠和雪貂体内引发了高水平的交叉反应和亚型特异性抗体，这些抗体对所有 20 种编码抗原都有反应。疫苗可以保护受到匹配和不匹配病毒株攻击的小鼠和雪貂，这种保护至少部分依赖于抗体。