Enhanced elicitation of potent neutralizing antibodies by the SARS-CoV-2 spike receptor binding domain Fc fusion protein in mice

Xianglei Liu; Aleksandra Drelich; Wei Li; Chuan Chen; Zehua Sun; Megan Shi; Cynthia Adams; John W. Mellors; Chien Te Tseng; Dimiter S. Dimitrov

doi:10.1016/j.vaccine.2020.09.058

Enhanced elicitation of potent neutralizing antibodies by the SARS-CoV-2 spike receptor binding domain Fc fusion protein in mice

Xianglei Liu, Aleksandra Drelich, Wei Li, Chuan Chen, Zehua Sun, Megan Shi, Cynthia Adams, John W. Mellors, Chien Te Tseng, Dimiter S. Dimitrov

Microbiology And Immunology

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

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.

Original language	English (US)
Pages (from-to)	7205-7212
Number of pages	8
Journal	Vaccine
Volume	38
Issue number	46
DOIs	https://doi.org/10.1016/j.vaccine.2020.09.058
State	Published - Oct 27 2020

Keywords

Cell–cell fusion assay
Receptor-binding domain (RBD)
SARS-CoV-2
Subunit vaccine

ASJC Scopus subject areas

Molecular Medicine
General Immunology and Microbiology
General Veterinary
Public Health, Environmental and Occupational Health
Infectious Diseases

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10.1016/j.vaccine.2020.09.058

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title = "Enhanced elicitation of potent neutralizing antibodies by the SARS-CoV-2 spike receptor binding domain Fc fusion protein in mice",

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.",

keywords = "Cell–cell fusion assay, Receptor-binding domain (RBD), SARS-CoV-2, Subunit vaccine",

author = "Xianglei Liu and Aleksandra Drelich and Wei Li and Chuan Chen and Zehua Sun and Megan Shi and Cynthia Adams and Mellors, {John W.} and Tseng, {Chien Te} and Dimitrov, {Dimiter S.}",

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doi = "10.1016/j.vaccine.2020.09.058",

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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.

PY - 2020/10/27

Y1 - 2020/10/27

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.

AB - 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.

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KW - Subunit vaccine

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Enhanced elicitation of potent neutralizing antibodies by the SARS-CoV-2 spike receptor binding domain Fc fusion protein in mice

Abstract

Keywords

ASJC Scopus subject areas

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