iScience (Jul 2023)
A nanobody recognizes a unique conserved epitope and potently neutralizes SARS-CoV-2 omicron variants
- Naphak Modhiran,
- Simon Malte Lauer,
- Alberto A. Amarilla,
- Peter Hewins,
- Sara Irene Lopes van den Broek,
- Yu Shang Low,
- Nazia Thakur,
- Benjamin Liang,
- Guillermo Valenzuela Nieto,
- James Jung,
- Devina Paramitha,
- Ariel Isaacs,
- Julian D.J. Sng,
- David Song,
- Jesper Tranekjær Jørgensen,
- Yorka Cheuquemilla,
- Jörg Bürger,
- Ida Vang Andersen,
- Johanna Himelreichs,
- Ronald Jara,
- Ronan MacLoughlin,
- Zaray Miranda-Chacon,
- Pedro Chana-Cuevas,
- Vasko Kramer,
- Christian Spahn,
- Thorsten Mielke,
- Alexander A. Khromykh,
- Trent Munro,
- Martina L. Jones,
- Paul R. Young,
- Keith Chappell,
- Dalan Bailey,
- Andreas Kjaer,
- Matthias Manfred Herth,
- Kellie Ann Jurado,
- David Schwefel,
- Alejandro Rojas-Fernandez,
- Daniel Watterson
Affiliations
- Naphak Modhiran
- School of Chemistry and Molecular Bioscience, the University of Queensland, Brisbane, QLD, Australia; Australian Institute for Bioengineering and Nanotechnology, Brisbane, QLD, Australia
- Simon Malte Lauer
- Institute of Medical Physics and Biophysics, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin, Germany
- Alberto A. Amarilla
- School of Chemistry and Molecular Bioscience, the University of Queensland, Brisbane, QLD, Australia
- Peter Hewins
- Department of Microbiology, University of Pennsylvania, Philadelphia, PA, USA
- Sara Irene Lopes van den Broek
- Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Jagtvej 160, 2100 Copenhagen, Denmark
- Yu Shang Low
- School of Chemistry and Molecular Bioscience, the University of Queensland, Brisbane, QLD, Australia
- Nazia Thakur
- The Pirbright Institute, Ash Road, Guildford, UK; Nuffield Department of Medicine, University of Oxford, Oxford, UK
- Benjamin Liang
- School of Chemistry and Molecular Bioscience, the University of Queensland, Brisbane, QLD, Australia
- Guillermo Valenzuela Nieto
- Institute of Medicine, Faculty of Medicine & Center for Interdisciplinary Studies on the Nervous System, CISNE, Universidad Austral de Chile, Valdivia, Chile
- James Jung
- School of Chemistry and Molecular Bioscience, the University of Queensland, Brisbane, QLD, Australia
- Devina Paramitha
- School of Chemistry and Molecular Bioscience, the University of Queensland, Brisbane, QLD, Australia
- Ariel Isaacs
- School of Chemistry and Molecular Bioscience, the University of Queensland, Brisbane, QLD, Australia
- Julian D.J. Sng
- School of Chemistry and Molecular Bioscience, the University of Queensland, Brisbane, QLD, Australia
- David Song
- Department of Microbiology, University of Pennsylvania, Philadelphia, PA, USA
- Jesper Tranekjær Jørgensen
- Department of Clinical Physiology, Nuclear Medicine & PET, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark; Cluster for Molecular Imaging, Department of Biomedical Sciences, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, Denmark
- Yorka Cheuquemilla
- Institute of Medicine, Faculty of Medicine & Center for Interdisciplinary Studies on the Nervous System, CISNE, Universidad Austral de Chile, Valdivia, Chile
- Jörg Bürger
- Institute of Medical Physics and Biophysics, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin, Germany; Microscopy and Cryo-Electron Microscopy Service Group, Max-Planck-Institute for Molecular Genetics, Berlin, Germany
- Ida Vang Andersen
- Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Jagtvej 160, 2100 Copenhagen, Denmark; Department of Clinical Physiology, Nuclear Medicine & PET, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark
- Johanna Himelreichs
- Institute of Medicine, Faculty of Medicine & Center for Interdisciplinary Studies on the Nervous System, CISNE, Universidad Austral de Chile, Valdivia, Chile
- Ronald Jara
- Institute of Medicine, Faculty of Medicine & Center for Interdisciplinary Studies on the Nervous System, CISNE, Universidad Austral de Chile, Valdivia, Chile
- Ronan MacLoughlin
- Research and Development, Science and Emerging Technologies, Aerogen Limited, Galway Business Park, H91 HE94 Galway, Ireland
- Zaray Miranda-Chacon
- Nuffield Department of Medicine, University of Oxford, Oxford, UK
- Pedro Chana-Cuevas
- CETRAM & Faculty of Medical Science Universidad de Santiago de Chile, Chile
- Vasko Kramer
- PositronPharma SA, Rancagua 878, 7500921 Providencia, Santiago, Chile
- Christian Spahn
- Institute of Medical Physics and Biophysics, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin, Germany
- Thorsten Mielke
- Microscopy and Cryo-Electron Microscopy Service Group, Max-Planck-Institute for Molecular Genetics, Berlin, Germany
- Alexander A. Khromykh
- School of Chemistry and Molecular Bioscience, the University of Queensland, Brisbane, QLD, Australia; Australian Infectious Diseases Research Centre, Global Virus Network Centre of Excellence, Brisbane, QLD, Australia
- Trent Munro
- Australian Institute for Bioengineering and Nanotechnology, Brisbane, QLD, Australia
- Martina L. Jones
- Australian Institute for Bioengineering and Nanotechnology, Brisbane, QLD, Australia
- Paul R. Young
- School of Chemistry and Molecular Bioscience, the University of Queensland, Brisbane, QLD, Australia; Australian Institute for Bioengineering and Nanotechnology, Brisbane, QLD, Australia; Australian Infectious Diseases Research Centre, Global Virus Network Centre of Excellence, Brisbane, QLD, Australia
- Keith Chappell
- School of Chemistry and Molecular Bioscience, the University of Queensland, Brisbane, QLD, Australia; Australian Institute for Bioengineering and Nanotechnology, Brisbane, QLD, Australia; Australian Infectious Diseases Research Centre, Global Virus Network Centre of Excellence, Brisbane, QLD, Australia
- Dalan Bailey
- The Pirbright Institute, Ash Road, Guildford, UK
- Andreas Kjaer
- Department of Clinical Physiology, Nuclear Medicine & PET, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark; Cluster for Molecular Imaging, Department of Biomedical Sciences, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, Denmark
- Matthias Manfred Herth
- Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Jagtvej 160, 2100 Copenhagen, Denmark; Department of Clinical Physiology, Nuclear Medicine & PET, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark
- Kellie Ann Jurado
- Department of Microbiology, University of Pennsylvania, Philadelphia, PA, USA
- David Schwefel
- Institute of Medical Physics and Biophysics, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin, Germany; Corresponding author
- Alejandro Rojas-Fernandez
- Nuffield Department of Medicine, University of Oxford, Oxford, UK; Berking Biotechnology, Valdivia, Chile; Corresponding author
- Daniel Watterson
- School of Chemistry and Molecular Bioscience, the University of Queensland, Brisbane, QLD, Australia; Australian Institute for Bioengineering and Nanotechnology, Brisbane, QLD, Australia; Australian Infectious Diseases Research Centre, Global Virus Network Centre of Excellence, Brisbane, QLD, Australia; Corresponding author
- Journal volume & issue
-
Vol. 26,
no. 7
p. 107085
Abstract
Summary: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) Omicron variant sub-lineages spread rapidly worldwide, mostly due to their immune-evasive properties. This has put a significant part of the population at risk for severe disease and underscores the need for effective anti-SARS-CoV-2 agents against emergent strains in vulnerable patients. Camelid nanobodies are attractive therapeutic candidates due to their high stability, ease of large-scale production, and potential for delivery via inhalation. Here, we characterize the receptor binding domain (RBD)-specific nanobody W25 and show superior neutralization activity toward Omicron sub-lineages in comparison to all other SARS-CoV2 variants. Structure analysis of W25 in complex with the SARS-CoV2 spike glycoprotein shows that W25 engages an RBD epitope not covered by any of the antibodies previously approved for emergency use. In vivo evaluation of W25 prophylactic and therapeutic treatments across multiple SARS-CoV-2 variant infection models, together with W25 biodistribution analysis in mice, demonstrates favorable pre-clinical properties. Together, these data endorse W25 for further clinical development.
