Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability
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Abstract
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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SciScore for 10.1101/2020.05.12.088716: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization Safety and efficacy of monoclonal antibody VIS410 in adults with uncomplicated influenza A infection: Results from a randomized, double-blind, phase-2, placebo-controlled study. Blinding not detected. Power Analysis not detected. Sex as a biological variable COSCA1 (47-yearold male) and COSCA2 (44-year-old female) showed symptoms of an upper respiratory tract infection and mild pneumonia, respectively (Table 1). Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Several of these antibodies were able to potently inhibit live SARS-CoV-2 infection at concentrations as low as 0.007 µg/mL, making them … SciScore for 10.1101/2020.05.12.088716: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization Safety and efficacy of monoclonal antibody VIS410 in adults with uncomplicated influenza A infection: Results from a randomized, double-blind, phase-2, placebo-controlled study. Blinding not detected. Power Analysis not detected. Sex as a biological variable COSCA1 (47-yearold male) and COSCA2 (44-year-old female) showed symptoms of an upper respiratory tract infection and mild pneumonia, respectively (Table 1). Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Several of these antibodies were able to potently inhibit live SARS-CoV-2 infection at concentrations as low as 0.007 µg/mL, making them the most potent human SARS-CoV-2 antibodies described to date. SARS-CoV-2suggested: NoneIndeed, therapeutic antibody cocktails with a variety of specificities have been used successfully against Ebola virus disease (7) and are being tested widely in clinical trials for HIV-1 (28). HIV-1 (28suggested: NoneA hallmark of antibody diversity is the heavy chain complementarity determining region 3 (CDRH3). CDRH3suggested: NoneThe average length of CDRH3 in the naive human repertoire is 15 amino acids (34), but for a subset of influenza virus and HIV-1 broadly neutralizing antibodies, long CDRH3 regions of 20-35 amino acids are crucial for high affinity antigen-antibody interactions (35, 36). HIV-1 broadly neutralizing antibodies, long CDRH3suggested: NoneWith IC50s of 0.008 µg/mL the RBD-targeting antibodies COVA1-18 and COVA2-15, in particular, were remarkably potent while being quite different in other aspects such as their heavy chain V gene usage (VH3-66 vs. VH3-23), light chain usage (VL7-46 vs. VK2-30), HC sequence identity (77%) and CDRH3 length (12 vs. 22 amino acids). COVA2-15suggested: NoneIn conclusion, convalescent COVID-19 patients showed strong anti-SARS-CoV-2 S protein specific B cell responses and developed memory and antibody producing B cells that may have participated in the control of infection and the establishment of humoral immunity. anti-SARS-CoV-2 Ssuggested: NoneHuman monoclonal antibodies block the binding of SARS-CoV-2 spike protein to angiotensin converting enzyme 2 receptor. angiotensin converting enzyme 2 receptor.suggested: NoneIdentification of human neutralizing antibodies against MERS-CoV and their role in virus adaptive evolution. human neutralizing antibodies against MERS-CoVsuggested: NoneNat Commun 8, 15371 (2017). L. Yu, Y. Guan, Immunologic Basis for Long HCDR3s in Broadly Neutralizing Antibodies Against HIV-1. Front Immunol 5, 250 (2014). F. Chen, N. Tzarum, I. A. Wilson, M. Law, VH1-69 antiviral broadly neutralizing antibodies: genetics, structures, and relevance to rational vaccine design. VH1-69suggested: NoneAn HIV-1 antibody from an elite neutralizer implicates the fusion peptide as a site of vulnerability. HIV-1suggested: NoneExperimental Models: Cell Lines Sentences Resources Subsequently, all HC and LC pairs were transiently expressed in HEK 293T cells and screened for binding by ELISA to SARS-CoV-2 S protein. HEK 293Tsuggested: KCB Cat# KCB 200744YJ, CVCL_006384 mAbs that showed potent binding were selected for small-scale expression in HEK 293F cells and purified. HEK 293Fsuggested: CVCL_6642Software and Algorithms Sentences Resources Structural and functional analysis of a potent sarbecovirus neutralizing antibody. bioRxiv, 2020.2004.2007.023903 (2020). X. Chen et al., bioRxivsuggested: (bioRxiv, SCR_003933)N. R. Voss, C. K. Yoshioka, M. Radermacher, C. S. Potter, B. Carragher, DoG Picker and TiltPicker: software tools to facilitate particle selection in single particle electron microscopy. TiltPickersuggested: (TiltPicker, SCR_016674)We did not find a statement about open data. We also did not find a statement about open code. Researchers are encouraged to share open data when possible (see Nature blog).
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