Center for Antibody Therapeutics, Division of Infectious Diseases, Department of Medicine, University of Pittsburgh Medical School, 3550 Terrace St, Pittsburgh, PA 15261, USA.
Department of Microbiology & Immunology, Centers for Biodefense and Emerging Diseases, Galveston National Laboratory, 301 University Blvd, Galveston, TX 77550, USA.
Vaccine. 2020 Oct 27;38(46):7205-7212. doi: 10.1016/j.vaccine.2020.09.058. Epub 2020 Sep 22.
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.
我们急需开发一种有效的 SARS-CoV-2 疫苗。我们生成了 SARS-CoV-2 RBD-Fc 融合蛋白，并评估了其在小鼠体内诱导中和抗体应答的效力。通过假病毒中和试验和基于活病毒的微量中和试验评估，RBD-Fc 诱导的中和抗体滴度高于 RBD。此外，通过定量细胞融合试验评估，RBD-Fc 免疫血清更好地抑制了细胞-细胞融合。细胞-细胞融合试验结果与病毒中和效力相关性良好，可用于在无需在生物安全三级实验室中使用活病毒感染的情况下，对大量抗 SARS-CoV-2 抗体和疫苗进行高通量筛选。此外，抗 RBD 血清并未增强假型 SARS-CoV-2 对 K562 细胞的感染。这些结果表明，Fc 融合可显著提高对重组 RBD 免疫原的体液免疫应答，并且表明 RBD-Fc 可作为针对 SARS-CoV-2 的有效疫苗的有用成分。
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