Open Biology (Jun 2024)
Structural and functional characterization of nanobodies that neutralize Omicron variants of SARS-CoV-2
- Katy Cornish,
- Jiandong Huo,
- Luke Jones,
- Parul Sharma,
- Joseph W. Thrush,
- Sahar Abdelkarim,
- Anja Kipar,
- Siva Ramadurai,
- Miriam Weckener,
- Halina Mikolajek,
- Sai Liu,
- Imogen Buckle,
- Eleanor Bentley,
- Adam Kirby,
- Ximeng Han,
- Stephen M. Laidlaw,
- Michelle Hill,
- Lauren Eyssen,
- Chelsea Norman,
- Audrey Le Bas,
- John Clarke,
- William James,
- James P. Stewart,
- Miles Carroll,
- James H. Naismith,
- Raymond J. Owens
Affiliations
- Katy Cornish
- Structural Biology, The Rosalind Franklin Institute, Harwell Science Campus , Didcot, UK
- Jiandong Huo
- Structural Biology, The Rosalind Franklin Institute, Harwell Science Campus , Didcot, UK
- Luke Jones
- Nuffield Department of Medicine, Pandemic Sciences Institute, University of Oxford , Oxford, UK
- Parul Sharma
- Department of Infection Biology & Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool , Liverpool, UK
- Joseph W. Thrush
- Structural Biology, The Rosalind Franklin Institute, Harwell Science Campus , Didcot, UK
- Sahar Abdelkarim
- Structural Biology, The Rosalind Franklin Institute, Harwell Science Campus , Didcot, UK
- Anja Kipar
- Department of Infection Biology & Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool , Liverpool, UK
- Siva Ramadurai
- Structural Biology, The Rosalind Franklin Institute, Harwell Science Campus , Didcot, UK
- Miriam Weckener
- Structural Biology, The Rosalind Franklin Institute, Harwell Science Campus , Didcot, UK
- Halina Mikolajek
- Diamond Light Source Ltd, Harwell Science Campus , Didcot, UK
- Sai Liu
- James & Lillian Martin Centre, Sir William Dunn School of Pathology, University of Oxford , Oxford, UK
- Imogen Buckle
- Structural Biology, The Rosalind Franklin Institute, Harwell Science Campus , Didcot, UK
- Eleanor Bentley
- Department of Infection Biology & Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool , Liverpool, UK
- Adam Kirby
- Department of Infection Biology & Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool , Liverpool, UK
- Ximeng Han
- Department of Infection Biology & Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool , Liverpool, UK
- Stephen M. Laidlaw
- Nuffield Department of Medicine, Pandemic Sciences Institute, University of Oxford , Oxford, UK
- Michelle Hill
- James & Lillian Martin Centre, Sir William Dunn School of Pathology, University of Oxford , Oxford, UK
- Lauren Eyssen
- Structural Biology, The Rosalind Franklin Institute, Harwell Science Campus , Didcot, UK
- Chelsea Norman
- Structural Biology, The Rosalind Franklin Institute, Harwell Science Campus , Didcot, UK
- Audrey Le Bas
- Structural Biology, The Rosalind Franklin Institute, Harwell Science Campus , Didcot, UK
- John Clarke
- Structural Biology, The Rosalind Franklin Institute, Harwell Science Campus , Didcot, UK
- William James
- James & Lillian Martin Centre, Sir William Dunn School of Pathology, University of Oxford , Oxford, UK
- James P. Stewart
- Department of Infection Biology & Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool , Liverpool, UK
- Miles Carroll
- Nuffield Department of Medicine, Pandemic Sciences Institute, University of Oxford , Oxford, UK
- James H. Naismith
- Structural Biology, The Rosalind Franklin Institute, Harwell Science Campus , Didcot, UK
- Raymond J. Owens
- Structural Biology, The Rosalind Franklin Institute, Harwell Science Campus , Didcot, UK
- DOI
- https://doi.org/10.1098/rsob.230252
- Journal volume & issue
-
Vol. 14,
no. 6
Abstract
The Omicron strains of SARS-CoV-2 pose a significant challenge to the development of effective antibody-based treatments as immune evasion has compromised most available immune therapeutics. Therefore, in the ‘arms race’ with the virus, there is a continuing need to identify new biologics for the prevention or treatment of SARS-CoV-2 infections. Here, we report the isolation of nanobodies that bind to the Omicron BA.1 spike protein by screening nanobody phage display libraries previously generated from llamas immunized with either the Wuhan or Beta spike proteins. The structure and binding properties of three of these nanobodies (A8, H6 and B5-5) have been characterized in detail providing insight into their binding epitopes on the Omicron spike protein. Trimeric versions of H6 and B5-5 neutralized the SARS-CoV-2 variant of concern BA.5 both in vitro and in the hamster model of COVID-19 following nasal administration. Thus, either alone or in combination could serve as starting points for the development of new anti-viral immunotherapeutics.
Keywords
