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Authors: Yan Wu et al.

Link to paper: https://www.medrxiv.org/content/10.1101/2020.05.01.20077743v1

Journal/ Pre-Print: Preprint from medRxiv (posted on 7th May, 2020)

Tags: Immunology/Immunity, Clinical/Diagnostics, Structural Biology, Therapeutics

Research Highlights 

1. A pair of monoclonal Ab isolated from COVID-19 patient can block binding of RBD protein to ACE2 receptor in vitro and reduce viral titre in a mouse model of infection.

2. The two identified neutralizing Ab recognize different epitopes on the RBD protein.

Summary 

Wu and colleagues describe two neutralizing monoclonal antibodies cloned from memory B cells of a COVID-19 patient. The Abs were shown to bind to separate epitopes on SARS-CoV2 RBD protein, block binding of RBD to ACE2 receptor and neutralize the virus in vitro. Administration to hACE2 transgenic mice challenged with SARS-Cov2 significantly reduced viral titre detected in lung tissue. A high-resolution crystal structure of one of the Abs in complex with RBD was determined to 1.9Å and detailed structural analysis is described. The study suggests the identified Abs could be promising candidates for the treatment of COVID-19.

Impact for SARS-CoV2/COVID19 research efforts

Develop a vaccine for SARS-CoV2/COVID19

Inhibit SARS-CoV2/COVID19 transmission

Treat SARS-CoV2/COVID19 positive individuals

Study Type

· In vitro study

· In vivo study (hACE2 transgenic mouse model)

Strengths and limitations of the paper

Novelty: Neutralizing monoclonal SARS-Cov-2 RBD-specific Abs isolated from COVID-19 patients have been reported already:

Potent human neutralizing antibodies elicited by SARS-CoV-2 infection, Bin Ju et al., posted on bioRxiv on 26th March, 2020.

However, this study is first to provide protective efficacy in vivo and detailed structural data on Ab-RBD complex.

Standing in the field: Not controversial.

Appropriate statistics: Inappropriate use of t-test for groups of 4 mice, needs a non-parametric test. No multiple comparison post-test used for 3b. Statistics for crystallography are in supplementary information.

Viral model used: Recombinant SARS-CoV2 RBD used as bait and SARS-CoV RBD used as a control (sequences accession numbers and aa boundaries reported)

SARS-CoV2 BetaCoV/shenzhen/SZTH-003/2020 strain used in the neutralization assay with Vero cells and HB-01 strain used in the animal experiment.

Translatability: High potential for translation into clinical application, reduction of viral load shown in vitro and in vivo in a mouse model.

Main limitations: It is strange that both H4 and B38 antibodies reduced viral load but only B38 reduced clinical symptoms in mice (body weight loss).

Reporting of viral load reduction by antibodies (“B38 group and H4 group reduction of 32.8% and 26% RNA copies change of that in PBS group, respectively”) seems wrong, as it is a log10 scale.