Structure-guided in vitro evolution of nanobodies targeting new viral variants

A major challenge in antiviral antibody therapy is keeping up with the rapid evolution of viruses. Our research shows that nanobodies - single-domain antibodies derived from camelids - can be rapidly re-engineered to combat new viral strains through structure-guided in vitro evolution. Specifically, for viral mutations occurring at nanobody-binding sites, we introduce randomized amino acid sequences into nanobody residues near these mutations. We then select nanobody variants that effectively bind to the mutated viral target from a phage display library. As a proof of concept, we used this approach to adapt Nanosota-3, a nanobody originally identified to target the receptor-binding domain (RBD) of early Omicron subvariants, making it highly effective against recent Omicron subvariants. Remarkably, this adaptation process can be completed in less than two weeks, allowing drug development to keep pace with viral evolution and provide timely protection to humans.

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Publication Details

Journal
PLoS Pathogens
Published
2024-09-26
DOI
https://doi.org/10.1371/journal.ppat.1012600
Citations
7
Primary Topic
Monoclonal and Polyclonal Antibodies Research
Type
article
Field-Weighted Citation Impact
2.83

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article

Structure-guided in vitro evolution of nanobodies targeting new viral variants

Bin Liu, Benjamin W. Spiller, Alise Mendoza, Stanley Perlman et al.
7 citations
PLoS Pathogens
Monoclonal and Polyclonal Antibodies Research
2.83
article

Structure-guided in vitro evolution of nanobodies targeting new viral variants

Bin Liu, Benjamin W. Spiller, Alise Mendoza, Stanley Perlman, Ruangang Pan, Lanying Du, Brian E. Wadzinski, Ge Yang, Fan Bu, Fang Li, Gang Ye
article en
7 citations

Abstract

A major challenge in antiviral antibody therapy is keeping up with the rapid evolution of viruses. Our research shows that nanobodies - single-domain antibodies derived from camelids - can be rapidly re-engineered to combat new viral strains through structure-guided in vitro evolution. Specifically, for viral mutations occurring at nanobody-binding sites, we introduce randomized amino acid sequences into nanobody residues near these mutations. We then select nanobody variants that effectively bind to the mutated viral target from a phage display library. As a proof of concept, we used this approach to adapt Nanosota-3, a nanobody originally identified to target the receptor-binding domain (RBD) of early Omicron subvariants, making it highly effective against recent Omicron subvariants. Remarkably, this adaptation process can be completed in less than two weeks, allowing drug development to keep pace with viral evolution and provide timely protection to humans.

PLoS PathogensVol. 20(9)
University of Iowa (US), University of Minnesota (US), Georgia State University (US), Vanderbilt University (US), Hormel (United States) (US), University of Minnesota Medical Center (US)
National Institutes of Health, National Institute of Allergy and Infectious Diseases
Good health and well-being
Openalex Percentile: Top 9%
Monoclonal and Polyclonal Antibodies Research
2.83
DOIOpen Access PDFOpenAlex
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