The SARS-CoV-2 receptor-binding domain elicits a potent neutralizing response without antibody-dependent enhancement
Open accessAbstract
SUMMARY: The SARS-coronavirus 2 (SARS-CoV-2) spike (S) protein mediates entry of SARS-CoV-2 into cells expressing the angiotensin-converting enzyme 2 (ACE2). The S protein engages ACE2 through its receptor-binding domain (RBD), an independently folded 197-amino acid fragment of the 1273-amino acid S-protein protomer. Antibodies to the RBD domain of SARS-CoV (SARS-CoV-1), a closely related coronavirus which emerged in 2002-2003, have been shown to potently neutralize SARS-CoV-1 S-protein-mediated entry, and the presence of anti-RBD antibodies correlates with neutralization in SARS-CoV-2 convalescent sera. Here we show that immunization with the SARS-CoV-2 RBD elicits a robust neutralizing antibody response in rodents, comparable to 100 µg/ml of ACE2-Ig, a potent SARS-CoV-2 entry inhibitor. Importantly, anti-sera from immunized animals did not mediate antibody-dependent enhancement (ADE) of S-protein-mediated entry under conditions in which Zika virus ADE was readily observed. These data suggest that an RBD-based vaccine for SARS-CoV-2 could be safe and effective.
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Immunization with recombinant RBD of SARS-CoV-2 induced high titers of neutralizing antibodies in the absence of antibody-dependent enhancement (ADE) of infection.
“Some recent studies also demonstrated that immunization with the recombinant RBD of SARS-CoV-2 induced high titers of neutralizing antibodies in the absence of antibody-dependent enhancement (ADE) of infection (Quinlan et al., 2020; Tai et al., 2020).”
From A thermostable mRNA vaccine against COVID-19 (2020) · cites this paper as Quinlan et al., 2020
Compared with full-length S protein, RBD antigen may induce fewer non-neutralizing antibodies, lowering the risk of potential ADE of SARS-CoV-2 infection.
“Compared with the full-length S protein, RBD antigen may induce fewer non-neutralizing antibodies, lowering the risk of potential ADE of SARS-CoV-2 infection”
From A thermostable mRNA vaccine against COVID-19 (2020) · cites this paper as Quinlan et al., 2020
Antibodies targeting the SARS-CoV-2 RBD at various concentrations did not induce ADE infection in a recent in vitro study.
“A recent in vitro study also suggests that antibodies targeting the SARS-CoV-2 RBD at various concentrations did not induce ADE infection (Quinlan et al., 2020).”
From A thermostable mRNA vaccine against COVID-19 (2020) · cites this paper as Quinlan et al., 2020
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References 57 · Cited by 140
Research works printed but not linked: 23
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- Authors
- Quinlan, B. D., Mou, H., Zhang, L., Guo, Y., He, W., Ojha, A., Parcells, M. S., Luo, G., Li, W., Zhong, G., Choe, H., & Farzan, M.
- Affiliations
- Scripps Research Institute (US)
- University of Delaware (US)
- University of Alabama at Birmingham (US)
- National Institute of Biological Sciences, Beijing (CN)
- Peking University (CN)
- Corresponding author
- Choe, Hyeryun
- Farzan, Michael
- ORCID
- Venue
- bioRxiv (Cold Spring Harbor Laboratory)
- Publisher
- openRxiv
- Published
- 2020-04-12
- OpenAlex
- W3016137283
- Cited by
- 140
- References
- 57
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 2 · 2023: 5 · 2022: 9 · 2021: 56 · 2020: 64
- Type
- posted content
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- SSRN Electronic Journal (acceptedVersion)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Keywords
- SARS-CoV-2, receptor binding domain, spike protein, neutralizing antibodies, antibody-dependent enhancement, vaccine immunization, ACE2, SARS-CoV-1, Zika virus, coronavirus entry, vaccine safety
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