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PreprintCited by 15SARS-CoV-2 and COVID-19 ResearchMonoclonal and Polyclonal Antibodies Researchvaccines and immunoinformatics approaches

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Optimizing a Human Monoclonal Antibody for Better Neutralization of SARS-CoV-2

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Wang, Qian, Guo, Yicheng, Casner, Ryan G., Yu, Jian, Nair, Manoj S., Ho, Jerren, Reddem, Eswar R., Mellis, Ian A., Wu, Madeline, Tzang, Chih Chen, Hong, Hsiang, Huang, Yaoxing, Shapiro, Lawrence, Liu, Lihong, Ho, David D.·2024·Nature Communications
DOI 10.1101/2024.12.04.626800PMC PMC12227675

Preprint — published as 10.1038/s41467-025-61472-z · Paper page

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Abstract

SARS-CoV-2 has largely evolved to resist antibody pressure, with each successive viral variant becoming more and more resistant to serum antibodies in the population. This evolution renders all previously authorized anti-spike therapeutic monoclonal antibodies inactive, and it threatens the remaining pipelines against COVID-19. We report herein the isolation of a human monoclonal antibody with a broad but incomplete SARS-CoV-2 neutralization profile, but structural analyses and mutational scanning lead to the engineering of variants that result in greater antibody flexibility while binding to the viral spike. Three such optimized monoclonal antibodies neutralize all SARS-CoV-2 strains tested with much improved potency and breadth, including against subvariants XEC and LP.8.1. The findings of this study not only present antibody candidates for clinical development against COVID-19, but also introduce a unique engineering approach to improve antibody activity via increasing conformational flexibility.

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Metadata

Authors
Wang, Q., Guo, Y., Casner, R. G., Yu, J., Nair, M. S., Ho, J., Reddem, E. R., Mellis, I. A., Wu, M., Tzang, C. C., Hong, H., Huang, Y., Shapiro, L., Liu, L., & Ho, D. D.
Affiliations
  • Aaron Diamond AIDS Research Center (US)
  • Mortimer B. Zuckerman Mind Brain Behavior Institute (US)
Corresponding author
  • Shapiro, Lawrence
  • Liu, Lihong
  • Ho, David D.
ORCID
Venue
Nature Communications
Publisher
openRxiv
Published
2024-12-05
Volume
16
Issue
1
Pages
6195-6195
ISSN
2041-1723 (ISSN-L)
DOI
10.1101/2024.12.04.626800
PMC
PMC12227675
OpenAlex
W4412020829
Cited by
15
References
1
Citations by year
2026: 8 · 2025: 7
FWCI
11.54
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Bill and Melinda Gates Foundation (INV-019355)
Topics
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Life Sciences › Immunology and Microbiology › Immunology › Monoclonal and Polyclonal Antibodies Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
Keywords
SARS-CoV-2, human monoclonal antibodies, antibody engineering, neutralizing antibodies, spike protein, Omicron subvariants, COVID-19 treatment, mutation scanning
MeSH terms
COVID-19, SARS-CoV-2, Animals, Antibodies, Monoclonal, Antibodies, Viral, Humans, Mutation, Neutralization Tests, Antibodies, Neutralizing, Spike Glycoprotein, Coronavirus

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