Enhanced Elicitation of Potent Neutralizing Antibodies by the SARS-CoV-2 Spike Receptor Binding Domain Fc Fusion Protein in Mice

Highlights • SARS-CoV-2 RBD-Fc elicited higher neutralizing antibodies titer than RBD as revealed by both pseudovirus and live virus microneutralization assays. • A newly developed high-throughput, quantitative cell-cell fusion assay showed a strong correlation with the neutralization assay. • Anti-RBD sera did not enhance the pseudotyped SARS-CoV-2 infection of K562 cells.
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.