Betacoronaviruses caused the outbreaks of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome, as well as the current pandemic of SARS coronavirus 2 (SARS-CoV-2)^1,2,3,4. Vaccines that elicit protective immunity against SARS-CoV-2 and betacoronaviruses that circulate in animals have the potential to prevent future pandemics. Here we show that the immunization of macaques with nanoparticles conjugated with the receptor-binding domain of SARS-CoV-2, and adjuvanted with 3M-052 and alum, elicits cross-neutralizing antibody responses against bat coronaviruses, SARS-CoV and SARS-CoV-2 (including the B.1.1.7, P.1 and B.1.351 variants). Vaccination of macaques with these nanoparticles resulted in a 50% inhibitory reciprocal serum dilution (ID₅₀) neutralization titre of 47,216 (geometric mean) for SARS-CoV-2, as well as in protection against SARS-CoV-2 in the upper and lower respiratory tracts. Nucleoside-modified mRNAs that encode a stabilized transmembrane spike or monomeric receptor-binding domain also induced cross-neutralizing antibody responses against SARS-CoV and bat coronaviruses, albeit at lower titres than achieved with the nanoparticles. These results demonstrate that current mRNA-based vaccines may provide some protection from future outbreaks of zoonotic betacoronaviruses, and provide a multimeric protein platform for the further development of vaccines against multiple (or all) betacoronaviruses.

Betacoronaviruses 导致了严重急性呼吸系统综合症 (SARS) 和中东呼吸系统综合症的爆发，以及当前的 SARS 冠状病毒 2 (SARS-CoV-2) ^1,2,3,4大流行。引发针对 SARS-CoV-2 和在动物体内传播的 β 冠状病毒的保护性免疫的疫苗有可能预防未来的大流行。在这里，我们展示了用与 SARS-CoV-2 的受体结合结构域缀合的纳米粒子免疫猕猴，并辅以 3M-052 和明矾，引发针对蝙蝠冠状病毒、SARS-CoV 和 SARS-CoV 的交叉中和抗体反应-2（包括 B.1.1.7、P.1 和 B.1.351 变体）。用这些纳米颗粒对猕猴进行疫苗接种导致 50% 抑制性血清稀释度（ID ₅₀) 对 SARS-CoV-2 的中和滴度为 47,216（几何平均值），以及在上呼吸道和下呼吸道中对 SARS-CoV-2 的保护作用。编码稳定的跨膜刺突或单体受体结合域的核苷修饰 mRNA 也诱导了针对 SARS-CoV 和蝙蝠冠状病毒的交叉中和抗体反应，尽管滴度低于纳米颗粒。这些结果表明，当前基于 mRNA 的疫苗可以为未来人畜共患 β 冠状病毒爆发提供一些保护，并为进一步开发针对多种（或全部）β 冠状病毒的疫苗提供多聚体蛋白平台。