Abstract—

Most vaccines work by inducing neutralizing antibodies that target the viral envelope. Enveloped RNA viruses have evolved mechanisms for surface glycoproteins to evade host immune responses, which exhibit substantial variability, even among different strains. Natural infection and vaccines using native forms of surface proteins may induce broadly neutralizing antibodies, yet with low and ineffective levels. Class I membrane-fusion proteins of enveloped RNA viruses, HIV-1, influenza A virus, SARS-CoV-2, yield a stable conformation (so-called “pre-fusion”) in providing fusion between viral and host cell membranes. Modified viral surface proteins that are based on these features induce neutralizing antibodies with activity available against a broad spectrum of circulating strains and make it possible to overcome the difficulties associated with escape/variability of viral antigen.

中文翻译：

---

包膜 RNA 病毒疫苗中刺突蛋白的修饰

摘要-

大多数疫苗通过诱导针对病毒包膜的中和抗体发挥作用。有包膜的RNA病毒已经进化出了表面糖蛋白逃避宿主免疫反应的机制，即使在不同的毒株之间，这种机制也表现出很大的变异性。使用天然形式的表面蛋白的自然感染和疫苗可能会诱导广泛的中和抗体，但水平较低且无效。有包膜RNA病毒、HIV-1、甲型流感病毒、SARS-CoV-2的I类膜融合蛋白在病毒和宿主细胞膜之间提供融合时产生稳定的构象（所谓的“预融合”）。基于这些特征的修饰病毒表面蛋白可诱导具有针对广谱流行病毒株活性的中和抗体，并使得克服与病毒抗原逃逸/变异相关的困难成为可能。