New Paper (Other): [Potent human neutralizing antibodies elicited by SARS-CoV-2 infection]

[KhiabanianLab]

Title: Potent human neutralizing antibodies elicited by SARS-CoV-2 infection

General Information

Please paste a link to the paper or a citation here:

Link: https://www.biorxiv.org/content/10.1101/2020.03.21.990770v2

What is the paper's Manubot-style citation?

Citation: @doi:10.1101/2020.03.21.990770v2

Is this paper primarily relevant to Background or Pathogesis?

• [X] Background
• [ ] Pathogenesis
• [ ] Methods

Please list some keywords (3-10) that help identify the relevance of this paper to COVID-19

• Monoclonal specific antibodies
• Cross-reactive antibodies

Which areas of expertise are particularly relevant to the paper?

• [X] virology
• [ ] epidemiology
• [ ] biostatistics
• [X] immunology
• [ ] pharmacology
• [ ] other:

Summary

If you would like to submit a summary of the paper, please copy and paste the following into a comment.

Suggested questions to answer about each paper:

• What did they analyze? Isolation and characterization of 206 monoclonal antibodies (mAbs) specific to receptor-binding domain (RBD) derived from single B cells of eight SARS-CoV-2 infected individuals.
• What methods did they use? ELISA, etc.
• Does this paper study COVID-19, SARS-CoV-2, or a related disease and/or virus? Yes.
• What is the main finding (or a few main takeaways)? Patient-derived antibodies bind and neutralize activity against SARS-CoV-2 and some are specific to its RBD.
• What does this paper tell us about the background and/or diagnostics/therapeutics for COVID-19 / SARS-CoV-2? This paper suggests that antibody response to RBDs could be viral species-specific with important therapeutic potential.
• Do you have any concerns about methodology or the interpretation of these results beyond this analysis? Experts need to review the methodology.

Any comments or notes?

[nilswellhausen]

I reviewed that paper for my contribution to the "Neutralizing Antibodies" section. I think they raised some important points in this paper: 1) Cross-reactivity often occurs outside of the RBD of the Spike protein. This has important implications for when other groups look at cross-reactivity and only look at spike protein in general. This also suggests that neutralizing antibodies developed for SARS-CoV and MERS-CoV will not work despite the similarity in protein structure. 2) Binding affinity does not reflect the capability to outcompete ACE2 binding 3) Neutralizing antibodies did not correlate with patient disease status.

Number 3 being the most significant one. Especially they mentioned that the patients with more severe disease actually had more potent neutralizing antibodies. This is also mentioned in this study here https://insight.jci.org/articles/view/123158. This begs the question of how useful their findings are in terms of therapeutic potential. They have not shown that these antibodies can protect a mouse or a human from infection or any other in vivo challenge. Until then, they only found antibodies that bind the target they screened for (they only looked for the RBD, nothing else) and inhibit ACE2 binding in vitro.