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Enhanced elicitation of potent neutralizing antibodies by the SARS-CoV-2 spike receptor binding domain Fc fusion protein in mice.
Vaccine. 2020 10 27; 38(46):7205-7212.V

Abstract

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.

Authors+Show Affiliations

Center for Antibody Therapeutics, Division of Infectious Diseases, Department of Medicine, University of Pittsburgh Medical School, 3550 Terrace St, Pittsburgh, PA 15261, USA. Electronic address: xil225@pitt.edu.Department of Microbiology & Immunology, Centers for Biodefense and Emerging Diseases, Galveston National Laboratory, 301 University Blvd, Galveston, TX 77550, USA.Center for Antibody Therapeutics, Division of Infectious Diseases, Department of Medicine, University of Pittsburgh Medical School, 3550 Terrace St, Pittsburgh, PA 15261, USA.Center for Antibody Therapeutics, Division of Infectious Diseases, Department of Medicine, University of Pittsburgh Medical School, 3550 Terrace St, Pittsburgh, PA 15261, USA.Center for Antibody Therapeutics, Division of Infectious Diseases, Department of Medicine, University of Pittsburgh Medical School, 3550 Terrace St, Pittsburgh, PA 15261, USA.Center for Antibody Therapeutics, Division of Infectious Diseases, Department of Medicine, University of Pittsburgh Medical School, 3550 Terrace St, Pittsburgh, PA 15261, USA.Center for Antibody Therapeutics, Division of Infectious Diseases, Department of Medicine, University of Pittsburgh Medical School, 3550 Terrace St, Pittsburgh, PA 15261, USA.Center for Antibody Therapeutics, Division of Infectious Diseases, Department of Medicine, University of Pittsburgh Medical School, 3550 Terrace St, Pittsburgh, PA 15261, USA; Abound Bio, 1401 Forbes Ave, Pittsburgh, PA 15219, USA.Department of Microbiology & Immunology, Centers for Biodefense and Emerging Diseases, Galveston National Laboratory, 301 University Blvd, Galveston, TX 77550, USA.Center for Antibody Therapeutics, Division of Infectious Diseases, Department of Medicine, University of Pittsburgh Medical School, 3550 Terrace St, Pittsburgh, PA 15261, USA; Abound Bio, 1401 Forbes Ave, Pittsburgh, PA 15219, USA. Electronic address: mit666666@pitt.edu.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33010978

Citation

Liu, Xianglei, et al. "Enhanced Elicitation of Potent Neutralizing Antibodies By the SARS-CoV-2 Spike Receptor Binding Domain Fc Fusion Protein in Mice." Vaccine, vol. 38, no. 46, 2020, pp. 7205-7212.
Liu X, Drelich A, Li W, et al. Enhanced elicitation of potent neutralizing antibodies by the SARS-CoV-2 spike receptor binding domain Fc fusion protein in mice. Vaccine. 2020;38(46):7205-7212.
Liu, X., Drelich, A., Li, W., Chen, C., Sun, Z., Shi, M., Adams, C., Mellors, J. W., Tseng, C. T., & Dimitrov, D. S. (2020). Enhanced elicitation of potent neutralizing antibodies by the SARS-CoV-2 spike receptor binding domain Fc fusion protein in mice. Vaccine, 38(46), 7205-7212. https://doi.org/10.1016/j.vaccine.2020.09.058
Liu X, et al. Enhanced Elicitation of Potent Neutralizing Antibodies By the SARS-CoV-2 Spike Receptor Binding Domain Fc Fusion Protein in Mice. Vaccine. 2020 10 27;38(46):7205-7212. PubMed PMID: 33010978.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Enhanced elicitation of potent neutralizing antibodies by the SARS-CoV-2 spike receptor binding domain Fc fusion protein in mice. AU - Liu,Xianglei, AU - Drelich,Aleksandra, AU - Li,Wei, AU - Chen,Chuan, AU - Sun,Zehua, AU - Shi,Megan, AU - Adams,Cynthia, AU - Mellors,John W, AU - Tseng,Chien-Te, AU - Dimitrov,Dimiter S, Y1 - 2020/09/22/ PY - 2020/06/17/received PY - 2020/08/19/revised PY - 2020/09/20/accepted PY - 2020/10/5/pubmed PY - 2020/11/3/medline PY - 2020/10/4/entrez KW - Cell–cell fusion assay KW - Receptor-binding domain (RBD) KW - SARS-CoV-2 KW - Subunit vaccine SP - 7205 EP - 7212 JF - Vaccine JO - Vaccine VL - 38 IS - 46 N2 - 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. SN - 1873-2518 UR - https://www.unboundmedicine.com/medline/citation/33010978/Enhanced_elicitation_of_potent_neutralizing_antibodies_by_the_SARS_CoV_2_spike_receptor_binding_domain_Fc_fusion_protein_in_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0264-410X(20)31229-9 DB - PRIME DP - Unbound Medicine ER -