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A human monoclonal antibody blocking SARS-CoV-2 infection

Authors: Chunyan Wang et al.

Link to paper: https://www.biorxiv.org/content/10.1101/2020.03.11.987958v1.full.pdf

Journal/ Pre-Print: medRxiv and bioRxiv

Key Words: Cross-neutralising Abs, SARS-CoV-2, SARS-CoV, MERS-CoV, neutralisation assay, ELISA, hybridoma.

Research Highlights

1. The humanized 47D11 antibody binds to cells expressing the full-length spike proteins of SARS-CoV and SARS-CoV-2.

2. Authentic infection of VeroE6 cells with SARS-CoV and SARS-CoV-2 was neutralized with 47D11 humanized mAb.

3. Binding of the neutralizing Ab 47D11 to SARS-S1B and SARS2-S1B did not stop S1B from binding to either soluble or membrane ACE2 receptor.

Summary 

The authors made and characterised a humanized monoclonal antibody that neutralized SARS-Cov-2 and SARS-CoV in vitro. This antibody was identified from H2H2 mice transgenic for human variable heavy and light chains that were immunized with SARS Spike (SARS-S). The 47D11 antibody which bound the receptor binding domain (S1B) was expressed as fully human IgG1. Binding affinity of 47D11 for SARS-S1B and SARS2-S1B was similar (16.1 and 9.6 nM). 47D11 impaired SARS-S and SARS2-S mediated syncytia formation. However, despite binding the receptor binding domain, 47D11 did not compete with ACE2 binding. Therefore, 47D11 neutralizes SARS-CoV and SARS-CoV-2 through an unknown mechanism that differs from receptor binding interference.

Impact for SARS-CoV2/COVID19 research efforts

Develop diagnostic tools for SARS-CoV2/COVID19 : This study shows a high-affinity antibody clone against the SARS-CoV2 S1B protein This antibody can be potentially useful for development of antigen detection tests and serological assays targeting SARS-CoV-2.

Study Type

· In vitro study

· In vivo study

Strengths and limitations of the paper

Novelty: 1. 47D11 bound the S1B of both viruses with similar affinities

2. Binding affinity of 47D11 for the spike ectodomain of SARS-CoV was higher relative to that of SARS-CoV-2.

3. Binding affinity of 47D11 for the SARS-S1B and SARS2-S1B was in a similar range (16.1 and 9.6 nM).

4. 47D11 was shown to impair SARS-S and SARS2-S mediated syncytia formation.

 

Standing in the field: Somewhat controversial results as human case studies show that human monoclonal antibodies taken from plasma patients who recovered from CoVid19 specific RBD antibodies do not cross react with RBD of SARS-CoV or MERS-CoV.

Appropriate statistics: No statistical tests are used to determine significance. The main experiments were either repeated twice (Fig. 1a, b) or once with technical triplicates (Fig. 1c).

Viral model used: Full infectious virus infection, S-GFP-transfected cell syncytium formation, and S-pseudotyped SARS-CoV2 and SARS-CoV viral strains were studied. Other strains used as control included MERS-CoV.

Translatability: Requires further investigation including in-vivo models, to check whether this antibody is protective in vivo.

Main limitations: The study did not investigate binding capacity of Trimeric Subunit S1 C and D.

These results show that the human monocloanal 47D11 antibody neutralizes SARS-CoV and SARS-Cov-2 infectivity via unknown mechanism that is not receptor binding interference. Even though the alternative mechanisms were proposed, these remain to be tested in the context of SARS-CoV-2.