Characterization of neutralizing antibodies from a SARS-CoV-2 infected individual

By Emily Seydoux, Leah J. Homad, Anna J. MacCamy, K. R. Parks, N. Hurlburt, Madeleine F. Jennewein, N. Akins, A. Stuart, Yu-Hsin Wan, Junli Feng and 9 more. 2020

71 citations recorded by the source corpus.

B cells specific for the SARS-CoV-2 S envelope glycoprotein spike were isolated from a COVID-19-infected subject using a stabilized spike-derived ectodomain (S2P) twenty-one days post-infection. Forty-four S2P-specific monoclonal antibodies were generated, three of which bound to the receptor binding domain (RBD). The antibodies were minimally mutated from germline and were derived from different B cell lineages. Only two antibodies displayed neutralizing activity against SARS-CoV-2 pseudo-virus. The most potent antibody bound the RBD in a manner that prevented binding to the ACE2 receptor, while the other bound outside the RBD. Our study indicates that the majority of antibodies against the viral envelope spike that were generated during the first weeks of COVID-19 infection are non-neutralizing and target epitopes outside the RBD. Antibodies that disrupt the SARS-CoV-2 spike-ACE2 interaction can potently neutralize the virus without undergoing extensive maturation. Such antibodies have potential preventive/therapeutic potential and can serve as templates for vaccine-design. IN BRIEF SARS-CoV-2 infection leads to expansion of diverse B cells clones against the viral spike glycoprotein (S). The antibodies bind S with high affinity despite being minimally mutated. Thus, the development of neutralizing antibody responses by vaccination will require the activation of certain naïve B cells without requiring extensive somatic mutation. Highlights Analysis of early B cell response to SARS-CoV-2 spike protein Most antibodies target non-neutralizing epitopes Potent neutralizing mAb blocks the interaction of the S protein with ACE2 Neutralizing antibodies are minimally mutated

Subfields: Infectious Diseases, Molecular Biology, Oncology

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In Infectious Diseases

1. C. Hillyer

In Molecular Biology

1. Dan H. Poston
2. Charles M. Rice
3. Michel C. Nussenzweig

Citations in the corpus

• Structures of Human Antibodies Bound to SARS-CoV-2 Spike Reveal Common Epitopes and Recurrent Features of Antibodies (2020, unknown): “Other studies have also reported anti-SARS-CoV-2 mAbs derived from these genes (Brouwer et al., 2020; Cao et al., 2020; Chi et al., 2020; Ju et al., 2020; Rogers et al., 2020; Seydoux et al., 2020; Wu et al., 2020c; Zost et al., 2020).”
• Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants (2020, background): “Recent studies have shown that related, potently neutralizing monoclonal antibodies that recognize the SARS-CoV-2 receptor binding domain (RBD) are often elicited in SARS-CoV-2 infection (3-17).”
• Mapping Neutralizing and Immunodominant Sites on the SARS-CoV-2 Spike Receptor-Binding Domain by Structure-Guided High-Resolution Serology (2020, unknown): “These findings are consistent with a previous study of the potent MERS-CoV m336 mAb, which harbors a single somatic mutation in the heavy chain (Ying et al., 2015) as well as with recent COVID-19 reports (Ju et al., 2020; Seydoux et al., 2020).”
• Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding (2020, unknown): “In addition, the RBD is the target of the most potent anti-SARS-CoV-2 neutralizing antibodies identified to date (Cao et al., 2020; Ju et al., 2020; Pinto et al., 2020; Rogers et al., 2020; Seydoux et al., 2020; Shi et al., 2020; Wu et al., 2020; Zost et al., 2020), and several promising vaccine can”