Nanobody repertoire generated against the spike protein of ancestral SARS-CoV-2 remains efficacious against the rapidly evolving virus
Open accessPreprint — published as 10.7554/elife.89423.3 · Paper page
Abstract
To date, all major modes of monoclonal antibody therapy targeting SARS-CoV-2 have lost significant efficacy against the latest circulating variants. As SARS-CoV-2 omicron sublineages account for over 90% of COVID-19 infections, evasion of immune responses generated by vaccination or exposure to previous variants poses a significant challenge. A compelling new therapeutic strategy against SARS-CoV-2 is that of single domain antibodies, termed nanobodies, which address certain limitations of monoclonal antibodies. Here we demonstrate that our high-affinity nanobody repertoire, generated against wild-type SARS-CoV-2 spike protein (Mast, Fridy et al. 2021), remains effective against variants of concern, including omicron BA.4/BA.5; a subset is predicted to counter resistance in emerging XBB and BQ.1.1 sublineages. Furthermore, we reveal the synergistic potential of nanobody cocktails in neutralizing emerging variants. Our study highlights the power of nanobody technology as a versatile therapeutic and diagnostic tool to combat rapidly evolving infectious diseases such as SARS-CoV-2.
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- Authors
- Ketaren, N. E., Mast, F. D., Fridy, P. C., Olivier, J. P., Sanyal, T., Sali, A., Chait, B. T., Rout, M. P., & Aitchison, J. D.
- Affiliations
- Rockefeller University (US)
- Seattle Children's Research Institute (US)
- QB3 (US)
- University of Washington (US)
- Corresponding author
- Chait, Brian T.
- Rout, Michael P.
- Aitchison, John D.
- ORCID
- Venue
- bioRxiv (Cold Spring Harbor Laboratory)
- Publisher
- openRxiv
- Published
- 2023-07-14
- PMC
- PMC10369967
- OpenAlex
- W4384283029
- Cited by
- 1
- References
- 8
- Citations by year
- 2025: 1
- Type
- posted content
- Language
- en
- Open access
- green
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion, cc-by-nc-nd)
- Funders
- Jain Foundation
- National Institutes of Health
- National Institute of General Medical Sciences (R01GM083960, P41GM109824)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 detection and testing
- Keywords
- nanobodies, SARS-CoV-2 spike protein, Omicron variant, BA.4/BA.5, XBB, BQ.1.1, neutralizing antibodies, COVID-19 treatment
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