The development of an effective vaccine against SARS-CoV-2 is urgently needed. We generated SARS-CoV-2 RBD-Fc fusion protein and evaluated its potency to elicit neutralizing antibody response in mice. RBD-Fc elicited a higher neutralizing antibodies titer than RBD as evaluated by a pseudovirus neutralization assay and a live virus based microneutralization assay. Furthermore, RBD-Fc immunized sera better inhibited cell–cell fusion, as evaluated by a quantitative cell–cell fusion assay. The cell–cell fusion assay results correlated well with the virus neutralization potency and could be used for high-throughput screening of large panels of anti-SARS-CoV-2 antibodies and vaccines without the requirement of live virus infection in BSL3 containment. Moreover, the anti-RBD sera did not enhance the pseudotyped SARS-CoV-2 infection of K562 cells. These results demonstrate that Fc fusion can significantly improve the humoral immune response to recombinant RBD immunogen, and suggest that RBD-Fc could serve as a useful component of effective vaccines against SARS-CoV-2.

迫切需要开发针对 SARS-CoV-2 的有效疫苗。我们生成了 SARS-CoV-2 RBD-Fc 融合蛋白，并评估了其在小鼠中引发中和抗体反应的效力。RBD-Fc 引发比 RBD 更高的中和抗体滴度，如通过假病毒中和测定和基于活病毒的微量中和测定所评估的。此外，RBD-Fc 免疫血清更好地抑制细胞-细胞融合，正如通过定量细胞-细胞融合测定所评估的那样。细胞-细胞融合试验结果与病毒中和效力密切相关，可用于高通量筛选大量抗 SARS-CoV-2 抗体和疫苗，而无需在 BSL3 封闭中感染活病毒。此外，抗 RBD 血清不会增强 K562 细胞的假型 SARS-CoV-2 感染。