Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability

By P. Brouwer, Tom G. Caniels, K. van der Straten, Jonne L. Snitselaar, Y. Aldon, S. Bangaru, J. Torres, Nisreen M. A. Okba, M. Claireaux, G. Kerster and 23 more. 2020

1,184 citations recorded by the source corpus.

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 Isolation of 403 monoclonal antibodies from COVID-19 patients revealed convergent gene usage and multiple target epitopes. The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a large impact on global health, travel, and economy. Therefore, preventative and therapeutic measures are urgently needed. Here, we isolated monoclonal antibodies from three convalescent coronavirus disease 2019 (COVID-19) patients using a SARS-CoV-2 stabilized prefusion spike protein. These antibodies had low levels of somatic hypermutation and showed a strong enrichment in VH1-69, VH3-30-3, and VH1-24 gene usage. A subset of the antibodies was able to potently inhibit authentic SARS-CoV-2 infection at a concentration as low as 0.007 micrograms per milliliter. Competition and electron microscopy studies illustrate that the SARS-CoV-2 spike protein contains multiple distinct antigenic sites, including several receptor-binding domain (RBD) epitopes as well as non-RBD epitopes. In addition to providing guidance for vaccine design, the antibodies described here are promising candidates for COVID-19 treatment and prevention.

Subfields: Infectious Diseases

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Infectious Diseases

1. Jesse D. Bloom
2. Wenshuai Wang
3. Anna Marie Pyle

Citations in the corpus

• Elicitation of Potent Neutralizing Antibody Responses by Designed Protein Nanoparticle Vaccines for SARS-CoV-2 (2020, neutral): “These findings showed that the RBD is a prime target of neutralizing Abs upon natural CoV infection, in agreement with reports of the isolation of RBD-targeted neutralizing Abs from COVID-19 convalescent patients (Barnes et al., 2020; Brouwer et al., 2020; Robbiani et al., 2020; Seydoux et al., 2020”
• Complete mapping of mutations to the SARS-CoV-2 spike receptor-binding domain that escape antibody recognition (2020, neutral): “…the RBM (Figure 2A,C), consistent with prior studies showing that potent anti-RBD neutralizing antibodies often strongly compete with ACE2 binding (Brouwer et al., 2020; Cao et al., 2020; Huang et al., 2020; Ju et al., 2020; Liu et al., 2020; Rogers et al., 2020; Seydoux et al., 2020; Wec et al.,…”
• Adaptive immunity to SARS-CoV-2 and COVID-19 (2021, neutral): “…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…”
• Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding (2020, neutral): “Mutational constraint of antibody epitopes The RBD is the dominant target of neutralizing antibodies to SARS-CoV-2 (Brouwer et al., 2020; Cao et al., 2020; Ju et al., 2020; Premkumar et al., 2020; Rogers et al., 2020; Suthar et al., 2020; Yuan et al., 2020a; Zhang et al., 2020; Zost et al., 2020).”
• GenSLMs: Genome-scale language models reveal SARS-CoV-2 evolutionary dynamics (2022, background): “…specialists who examine variations, identify epitopes of interest (i.e., portions of the virus that elicit immune response), classify variants, and eventually flag them for further laboratory testing and analysis (Brouwer et al., 2020, Greaney et al., 2021, Ju et al., 2020, Zost et al., 2020).”
• Neutralizing and protective human monoclonal antibodies recognizing the N-terminal domain of the SARS-CoV-2 spike protein (2021, background): “Most neutralizing SARS-CoV-2 mAbs block RBD interactions with ACE2 (Brouwer et al., 2020; Cao et al., 2020; Ju et al., 2020; Liu et al., 2020a; Rogers et al., 2020; Seydoux et al., 2020; Wec et al., 2020; Wu et al., 2020; Zost et al., 2020a, 2020b).”