A human monoclonal antibody blocks SARS-CoV-2 in cell culture

An article published in Nature Communications reports a recombinantly expressed human chimeric 47D11 H2L2 antibody, reformatted to a fully human immunoglobulin that binded to cells expressing the full-length spike proteins of SARS-CoV and SARS-CoV-2 and could potently inhibit infection of VeroE6 cells with SARS-S and SARS2-S pseudotyped VSV.

Abstract

The emergence of the novel human coronavirus SARS-CoV-2 in Wuhan, China has caused a worldwide epidemic of respiratory disease (COVID-19). Vaccines and targeted therapeutics for treatment of this disease are currently lacking. Here we report a human monoclonal antibody that neutralizes SARS-CoV-2 (and SARS-CoV) in cell culture. This cross-neutralizing antibody targets a communal epitope on these viruses and may offer potential for prevention and treatment of COVID-19.

a Binding of 47D11 to HEK-293T cells expressing GFP-tagged spike proteins of SARS-CoV and SARS-CoV-2 detected by immunofluorescence assay. The human mAb 7.7G6 targeting the MERS-CoV S1_B spike domain was taken along as a negative control, cell nuclei in the overlay images are visualized with DAPI. b Antibody-mediated neutralization of infection of luciferase-encoding VSV particles pseudotyped with spike proteins of SARS-CoV and SARS-CoV-2. Pseudotyped VSV particles pre-incubated with antibodies at indicated concentrations (see Methods) were used to infect VeroE6 cells and luciferase activities in cell lysates were determined at 24 h post transduction to calculate infection (%) relative to non-antibody-treated controls. The average ± SD from at least three independent experiments with technical triplicates is shown. Iso-CTRL: an anti-Strep-tag human monoclonal antibody¹¹ was used as an antibody isotype control. c Antibody-mediated neutralization of SARS-CoV and SARS-CoV-2 infection on VeroE6 cells. The experiment was performed with triplicate samples, the average ± SD is shown. Source data are provided as a Source Data file.

Wang, C., Li, W., Drabek, D. et al. A human monoclonal antibody blocking SARS-CoV-2 infection. Nat Commun11, 2251 (2020). https://doi.org/10.1038/s41467-020-16256-y

Abstract

Background: Recently, several potent human monoclonal antibodies (hmAbs) targeting the severe acute respiratory syndrome-associated coronavirus (SARS CoV) S glycoproteins, as well as the first fully human mAbs against two other paramyxoviruses, Hendra virus (HeV) and Nipah virus (NiV) have been discovered. Objective: To examine, compare and contrast the functional characteristics of hmAbs with potential for prophylaxis and treatment of diseases caused by SARS CoV, HeV and NiV. Methods: A review of relevant literature. Results/conclusions: Structural analyses have provided insights into the molecular mechanisms of receptor recognition and antibody neutralization, and suggested that these antibodies alone or in combination could fight the viruses' heterogeneity and mutability, which is a major problem in the development of effective therapeutic agents against viruses, including therapeutic antibodies.

Ponraj Prabakaran, Zhongyu Zhu, Xiaodong Xiao, Arya Biragyn, Antony S Dimitrov, Christopher C Broder & Dimiter S Dimitrov (2009) Potent human monoclonal antibodies against SARS CoV, Nipah and Hendra viruses, Expert Opinion on Biological Therapy, 9:3, 355-368, DOI: 10.1517/14712590902763755

https://www.tandfonline.com/doi/full/10.1517/14712590902763755

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