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Mapping cross-variant neutralizing sites on the SARS-CoV-2 spike protein.
- Source :
-
Emerging microbes & infections [Emerg Microbes Infect] 2022 Dec; Vol. 11 (1), pp. 351-367. - Publication Year :
- 2022
-
Abstract
- The emergence of multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern threatens the efficacy of currently approved vaccines and authorized therapeutic monoclonal antibodies (MAbs). It is hence important to continue searching for SARS-CoV-2 broadly neutralizing MAbs and defining their epitopes. Here, we isolate 9 neutralizing mouse MAbs raised against the spike protein of a SARS-CoV-2 prototype strain and evaluate their neutralizing potency towards a panel of variants, including B.1.1.7, B.1.351, B.1.617.1, and B.1.617.2. By using a combination of biochemical, virological, and cryo-EM structural analyses, we identify three types of cross-variant neutralizing MAbs, represented by S5D2, S5G2, and S3H3, respectively, and further define their epitopes. S5D2 binds the top lateral edge of the receptor-binding motif within the receptor-binding domain (RBD) with a binding footprint centred around the loop <superscript>477-489</superscript> , and efficiently neutralizes all variant pseudoviruses, but the potency against B.1.617.2 was observed to decrease significantly. S5G2 targets the highly conserved RBD core region and exhibits comparable neutralization towards the variant panel. S3H3 binds a previously unreported epitope located within the evolutionarily stable SD1 region and is able to near equally neutralize all of the variants tested. Our work thus defines three distinct cross-variant neutralizing sites on the SARS-CoV-2 spike protein, providing guidance for design and development of broadly effective vaccines and MAb-based therapies.
- Subjects :
- Animals
Antibodies, Neutralizing immunology
Antibodies, Viral immunology
COVID-19 immunology
Epitope Mapping
Female
Humans
Mice
Mice, Inbred BALB C
Neutralization Tests
SARS-CoV-2 chemistry
SARS-CoV-2 genetics
Spike Glycoprotein, Coronavirus genetics
COVID-19 virology
SARS-CoV-2 immunology
Spike Glycoprotein, Coronavirus chemistry
Spike Glycoprotein, Coronavirus immunology
Subjects
Details
- Language :
- English
- ISSN :
- 2222-1751
- Volume :
- 11
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Emerging microbes & infections
- Publication Type :
- Academic Journal
- Accession number :
- 34964428
- Full Text :
- https://doi.org/10.1080/22221751.2021.2024455