Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability
Open accessPublished version of a preprint
Abstract
Sites of vulnerability in SARS-CoV-2: Antibodies that neutralize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could be an important tool in treating coronavirus disease 2019 (COVID-19). Brouwer et al. isolated 403 monoclonal antibodies from three convalescent COVID-19 patients. They show that the patients had strong immune responses against the viral spike protein, a complex that binds to receptors on the host cell. A subset of antibodies was able to neutralize the virus. Competition and electron microscopy studies showed that these antibodies target diverse epitopes on the spike, with the two most potent targeting the domain that binds the host receptor. Science , this issue p. 643
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Most of the strongest neutralizing antibodies against SARS-CoV-2 identified so far bind the RBD.
“We focused on the RBD since it is the target of the majority of the more potent SARS-CoV-2 neutralizing antibodies discovered to date21–26.”
From mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants (2021) · cites this paper as [22]
Antibodies in classes 1 and 2 are both highly potent and highly abundant.
“Class 1 and 2 antibodies are among the most potent and also the most abundant antibodies7,8,21,22,25,39.”
From mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants (2021) · cites this paper as [22]
mRNA vaccines induce antibodies to RBD, the main target of neutralizing antibodies, in a way that resembles natural infection.
“The vaccines elicit antibody responses against the RBD, the major target of neutralizing antibodies21–26, in a manner that resembles natural infection.”
From mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants (2021) · cites this paper as [22]
Plasma RBD antibodies are strongly correlated with neutralizing activity.
“We limited our analysis to RBD because plasma RBD antibodies are strongly correlated with neutralizing activity3,10–12.”
From Naturally enhanced neutralizing breadth against SARS-CoV-2 one year after infection (2021) · cites this paper as [10]
All S constructs were verified by Sanger sequencing.
“All S constructs were cloned into a pPPI4 expression vector containing a His tag, verified by Sanger sequencing and subsequently produced in human embryonic kidney–293F cells, and purified as previously described (6, 80).”
From SARS-CoV-2 variants of concern partially escape humoral but not T cell responses in COVID-19 convalescent donors and vaccine recipients (2021) · cites this paper as [6]
SARS-CoV-2 infection rapidly elicits nAbs that decline, but remain detectable, over several months.
“SARS-CoV-2 infection rapidly elicits nAbs (16, 21–24) that decline, but remain detectable, over several months (25–29).”
From mRNA vaccination boosts cross-variant neutralizing antibodies elicited by SARS-CoV-2 infection (2021) · cites this paper as [24]
Numerous neutralizing anti-RBD monoclonal antibodies have been characterized, the most potent of which block the RBD-ACE2 interaction.
“Numerous neutralizing anti-RBD monoclonal antibodies (mAbs) have been characterized, the most potent of which block the RBD-ACE2 interaction (16, 17, 22–24, 32–37).”
From mRNA vaccination boosts cross-variant neutralizing antibodies elicited by SARS-CoV-2 infection (2021) · cites this paper as [24]
Neutralizing mAbs that bind regions of the viral spike have also been identified.
“Neutralizing mAbs that bind regions of the viral spike have also been identified (24, 33, 38–42).”
From mRNA vaccination boosts cross-variant neutralizing antibodies elicited by SARS-CoV-2 infection (2021) · cites this paper as [24]
The receptor binding domain of Spike is the target of more than 90% of neutralizing antibodies in COVID-19 cases, with some targeting the N-terminal domain.
“Spike is the target of SARS-CoV-2 neutralizing antibodies, and the receptor binding domain (RBD) of Spike is the target of >90% of neutralizing antibodies in COVID-19 cases (Brouwer et al., 2020; Piccoli et al., 2020; Robbiani et al., 2020; Rogers et al., 2020; Suthar et al., 2020), with some neutralizing antibodies instead targeting the N-terminal domain (NTD) (Liu et al., 2020).”
From Adaptive immunity to SARS-CoV-2 and COVID-19 (2021) · cites this paper as Brouwer et al., 2020
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References 58 · Cited by 1,140
Research works printed but not linked: 1
- [6]R. Kulkarni, in Dynamics of Immune Activation in Viral Diseases, P. V. Bramhachari, Ed. (Springer, 2020), pp. 9–41.
- Authors
- Brouwer, P. J. M., Caniels, T. G., van der Straten, K., Snitselaar, J. L., Aldon, Y., Bangaru, S., Torres, J. L., Okba, N. M. A., Claireaux, M., Kerster, G., Bentlage, A. E. H., van Haaren, M. M., Guerra, D., Burger, J. A., Schermer, E. E., Verheul, K. D., van der Velde, N., van der Kooi, A., van Schooten, J., van Breemen, M. J., Bijl, T. P. L., Sliepen, K., Aartse, A., Derking, R., Bontjer, I., Kootstra, N. A., Wiersinga, W. J., Vidarsson, G., Haagmans, B. L., Ward, A. B., de Bree, G. J., Sanders, R. W., & van Gils, M. J.
- Affiliations
- Amsterdam University Medical Centers (NL)
- Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105AZ Amsterdam, Netherlands.
- Scripps Research Institute (US)
- Erasmus MC (NL)
- Sanquin (NL)
- IBIS Technologies BV, 7521PR Enschede, Netherlands.
- Biomedical Primate Research Centre (NL)
- Department of Internal Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, 1105AZ Amsterdam, Netherlands.
- Cornell University (US)
- Corresponding author
- Sanders, Rogier W.
- ORCID
- Brouwer, Philip J. M.
- Caniels, Tom G.
- van der Straten, Karlijn
- Snitselaar, Jonne L.
- Aldon, Yoann
- Bangaru, Sandhya
- Torres, Jonathan L.
- Okba, Nisreen M. A.
- Claireaux, Mathieu
- Kerster, Gius
- Bentlage, Arthur E. H.
- Guerra, Denise
- Burger, Judith A.
- van der Kooi, Alex
- van Schooten, Jelle
- Sliepen, Kwinten
- Derking, Ronald
- Bontjer, Ilja
- Kootstra, Neeltje A.
- Wiersinga, W. Joost
- Vidarsson, Gestur
- Haagmans, Bart L.
- Ward, Andrew B.
- de Bree, Godelieve J.
- Sanders, Rogier W.
- van Gils, Marit J.
- Venue
- Science
- Published
- 2020-08-07
- Volume
- 369
- Issue
- 6504
- Pages
- 643-650
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC7299281
- OpenAlex
- W3034425032
- Cited by
- 1,140
- References
- 58
- Citations by year
- 2026: 32 · 2025: 63 · 2024: 77 · 2023: 137 · 2022: 230 · 2021: 430 · 2020: 170
- FWCI
- 31.77
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Science (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- HAL (submittedVersion)
- Funders
- Bill and Melinda Gates Foundation (OPP1111923, OPP1132237 and INV-002022)
- University of Amsterdam (proof of concept fund 200421, AMC Fellowship 2017, Amsterdam Infection and Immunity Institute COVID19 grant)
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek
- Fondation Dormeur, Vaduz
- Health Holland
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Keywords
- SARS-CoV-2, COVID-19 pandemic, neutralizing antibodies, monoclonal antibodies, somatic hypermutation, vaccine design, antibody therapy
- MeSH terms
- Protein Domains, Betacoronavirus, Broadly Neutralizing Antibodies, Receptors, Coronavirus, COVID-19, SARS-CoV-2, Adult, Aged, Antibodies, Monoclonal, Antibodies, Viral, Antibody Affinity, Epitopes, Antigens, Viral, Female, Humans, Immunologic Memory, Male, Middle Aged, Pneumonia, Viral, Receptors, Virus, Immunophenotyping, B-Lymphocyte Subsets, Coronavirus Infections, Cell Line, Tumor, Protein Interaction Domains and Motifs, Antibodies, Neutralizing, Pandemics, Spike Glycoprotein, Coronavirus
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