Monospecific and bispecific monoclonal SARS-CoV-2 neutralizing antibodies that maintain potency against B.1.617

13Citations
Citations of this article
41Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

COVID-19 pathogen SARS-CoV-2 has infected hundreds of millions and caused over 5 million deaths to date. Although multiple vaccines are available, breakthrough infections occur especially by emerging variants. Effective therapeutic options such as monoclonal antibodies (mAbs) are still critical. Here, we report the development, cryo-EM structures, and functional analyses of mAbs that potently neutralize SARS-CoV-2 variants of concern. By high-throughput single cell sequencing of B cells from spike receptor binding domain (RBD) immunized animals, we identify two highly potent SARS-CoV-2 neutralizing mAb clones that have single-digit nanomolar affinity and low-picomolar avidity, and generate a bispecific antibody. Lead antibodies show strong inhibitory activity against historical SARS-CoV-2 and several emerging variants of concern. We solve several cryo-EM structures at ~3 Å resolution of these neutralizing antibodies in complex with prefusion spike trimer ectodomain, and reveal distinct epitopes, binding patterns, and conformations. The lead clones also show potent efficacy in vivo against authentic SARS-CoV-2 in both prophylactic and therapeutic settings. We also generate and characterize a humanized antibody to facilitate translation and drug development. The humanized clone also has strong potency against both the original virus and the B.1.617.2 Delta variant. These mAbs expand the repertoire of therapeutics against SARS-CoV-2 and emerging variants.

References Powered by Scopus

UCSF Chimera - A visualization system for exploratory research and analysis

35318Citations
N/AReaders
Get full text

Features and development of Coot

21303Citations
N/AReaders
Get full text

A pneumonia outbreak associated with a new coronavirus of probable bat origin

15598Citations
N/AReaders
Get full text

Cited by Powered by Scopus

Applications of single-cell RNA sequencing in drug discovery and development

144Citations
N/AReaders
Get full text

Omicron-specific mRNA vaccination alone and as a heterologous booster against SARS-CoV-2

39Citations
N/AReaders
Get full text

Function and Cryo-EM structures of broadly potent bispecific antibodies against multiple SARS-CoV-2 Omicron sublineages

5Citations
N/AReaders
Get full text

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Cite

CITATION STYLE

APA

Peng, L., Hu, Y., Mankowski, M. C., Ren, P., Chen, R. E., Wei, J., … Chen, S. (2022). Monospecific and bispecific monoclonal SARS-CoV-2 neutralizing antibodies that maintain potency against B.1.617. Nature Communications, 13(1). https://doi.org/10.1038/s41467-022-29288-3

Readers over time

‘22‘23‘24‘2506121824

Readers' Seniority

Tooltip

PhD / Post grad / Masters / Doc 9

56%

Researcher 5

31%

Professor / Associate Prof. 2

13%

Readers' Discipline

Tooltip

Biochemistry, Genetics and Molecular Bi... 9

60%

Pharmacology, Toxicology and Pharmaceut... 2

13%

Medicine and Dentistry 2

13%

Immunology and Microbiology 2

13%

Save time finding and organizing research with Mendeley

Sign up for free
0