A safe, effective, and scalable vaccine is needed to halt the ongoing SARS-CoV-2 pandemic. We describe the structure-based design of self-assembling protein nanoparticle immunogens that elicit potent and protective antibody responses against SARS-CoV-2 in mice. The nanoparticle vaccines display 60 SARS-CoV-2 spike receptor-binding domains (RBDs) in a highly immunogenic array and induce neutralizing antibody titers 10-fold higher than the prefusion-stabilized spike despite a 5-fold lower dose. Antibodies elicited by the RBD nanoparticles target multiple distinct epitopes, suggesting they may not be easily susceptible to escape mutations, and exhibit a lower binding:neutralizing ratio than convalescent human sera, which may minimize the risk of vaccine-associated enhanced respiratory disease. The high yield and stability of the assembled nanoparticles suggest that manufacture of the nanoparticle vaccines will be highly scalable. These results highlight the utility of robust antigen display platforms and have launched cGMP manufacturing efforts to advance the SARS-CoV-2-RBD nanoparticle vaccine into the clinic.

需要一种安全、有效且可扩展的疫苗来阻止正在进行的 SARS-CoV-2 大流行。我们描述了基于结构的自组装蛋白纳米颗粒免疫原的设计，该免疫原可在小鼠体内引发针对 SARS-CoV-2 的有效且保护性的抗体反应。纳米颗粒疫苗在高免疫原性阵列中显示 60 个 SARS-CoV-2 刺突受体结合域 (RBD)，尽管剂量低 5 倍，但诱导的中和抗体滴度比灌注前稳定的刺突高 10 倍。RBD纳米粒子引发的抗体针对多个不同的表位，表明它们可能不容易受到逃逸突变的影响，并且表现出比恢复期人类血清更低的结合：中和比，这可以最大限度地降低疫苗相关的增强性呼吸道疾病的风险。组装纳米颗粒的高产率和稳定性表明纳米颗粒疫苗的生产将具有高度可扩展性。这些结果凸显了强大的抗原展示平台的实用性，并启动了 cGMP 生产工作，以将 SARS-CoV-2-RBD 纳米颗粒疫苗推向临床。