Development of molecular clamp stabilized hemagglutinin vaccines for Influenza A viruses
Abstract Influenza viruses cause a significant number of infections and deaths annually. In addition to seasonal infections, the risk of an influenza virus pandemic emerging is extremely high owing to the large reservoir of diverse influenza viruses found in animals and the co-circulation of many in...
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Nature Portfolio
2021
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oai:doaj.org-article:d088126b54144c22b6c71abe6699d6052021-11-14T12:07:48ZDevelopment of molecular clamp stabilized hemagglutinin vaccines for Influenza A viruses10.1038/s41541-021-00395-42059-0105https://doaj.org/article/d088126b54144c22b6c71abe6699d6052021-11-01T00:00:00Zhttps://doi.org/10.1038/s41541-021-00395-4https://doaj.org/toc/2059-0105Abstract Influenza viruses cause a significant number of infections and deaths annually. In addition to seasonal infections, the risk of an influenza virus pandemic emerging is extremely high owing to the large reservoir of diverse influenza viruses found in animals and the co-circulation of many influenza subtypes which can reassort into novel strains. Development of a universal influenza vaccine has proven extremely challenging. In the absence of such a vaccine, rapid response technologies provide the best potential to counter a novel influenza outbreak. Here, we demonstrate that a modular trimerization domain known as the molecular clamp allows the efficient production and purification of conformationally stabilised prefusion hemagglutinin (HA) from a diverse range of influenza A subtypes. These clamp-stabilised HA proteins provided robust protection from homologous virus challenge in mouse and ferret models and some cross protection against heterologous virus challenge. This work provides a proof-of-concept for clamp-stabilised HA vaccines as a tool for rapid response vaccine development against future influenza A virus pandemics.Christopher L. D. McMillanStacey T. M. CheungNaphak ModhiranJames BarnesAlberto A. AmarillaHelle Bielefeldt-OhmannLeo Yi Yang LeeKate GuilfoyleGeert van AmerongenKoert StittelaarVirginie JakonCelia LebasPatrick ReadingKirsty R. ShortPaul R. YoungDaniel WattersonKeith J. ChappellNature PortfolioarticleImmunologic diseases. AllergyRC581-607Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Vaccines, Vol 6, Iss 1, Pp 1-12 (2021) |
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Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 |
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Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Christopher L. D. McMillan Stacey T. M. Cheung Naphak Modhiran James Barnes Alberto A. Amarilla Helle Bielefeldt-Ohmann Leo Yi Yang Lee Kate Guilfoyle Geert van Amerongen Koert Stittelaar Virginie Jakon Celia Lebas Patrick Reading Kirsty R. Short Paul R. Young Daniel Watterson Keith J. Chappell Development of molecular clamp stabilized hemagglutinin vaccines for Influenza A viruses |
description |
Abstract Influenza viruses cause a significant number of infections and deaths annually. In addition to seasonal infections, the risk of an influenza virus pandemic emerging is extremely high owing to the large reservoir of diverse influenza viruses found in animals and the co-circulation of many influenza subtypes which can reassort into novel strains. Development of a universal influenza vaccine has proven extremely challenging. In the absence of such a vaccine, rapid response technologies provide the best potential to counter a novel influenza outbreak. Here, we demonstrate that a modular trimerization domain known as the molecular clamp allows the efficient production and purification of conformationally stabilised prefusion hemagglutinin (HA) from a diverse range of influenza A subtypes. These clamp-stabilised HA proteins provided robust protection from homologous virus challenge in mouse and ferret models and some cross protection against heterologous virus challenge. This work provides a proof-of-concept for clamp-stabilised HA vaccines as a tool for rapid response vaccine development against future influenza A virus pandemics. |
format |
article |
author |
Christopher L. D. McMillan Stacey T. M. Cheung Naphak Modhiran James Barnes Alberto A. Amarilla Helle Bielefeldt-Ohmann Leo Yi Yang Lee Kate Guilfoyle Geert van Amerongen Koert Stittelaar Virginie Jakon Celia Lebas Patrick Reading Kirsty R. Short Paul R. Young Daniel Watterson Keith J. Chappell |
author_facet |
Christopher L. D. McMillan Stacey T. M. Cheung Naphak Modhiran James Barnes Alberto A. Amarilla Helle Bielefeldt-Ohmann Leo Yi Yang Lee Kate Guilfoyle Geert van Amerongen Koert Stittelaar Virginie Jakon Celia Lebas Patrick Reading Kirsty R. Short Paul R. Young Daniel Watterson Keith J. Chappell |
author_sort |
Christopher L. D. McMillan |
title |
Development of molecular clamp stabilized hemagglutinin vaccines for Influenza A viruses |
title_short |
Development of molecular clamp stabilized hemagglutinin vaccines for Influenza A viruses |
title_full |
Development of molecular clamp stabilized hemagglutinin vaccines for Influenza A viruses |
title_fullStr |
Development of molecular clamp stabilized hemagglutinin vaccines for Influenza A viruses |
title_full_unstemmed |
Development of molecular clamp stabilized hemagglutinin vaccines for Influenza A viruses |
title_sort |
development of molecular clamp stabilized hemagglutinin vaccines for influenza a viruses |
publisher |
Nature Portfolio |
publishDate |
2021 |
url |
https://doaj.org/article/d088126b54144c22b6c71abe6699d605 |
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