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...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: 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
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2021
Materias:
Acceso en línea:https://doaj.org/article/d088126b54144c22b6c71abe6699d605
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:d088126b54144c22b6c71abe6699d605
record_format dspace
spelling 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)
institution DOAJ
collection DOAJ
language EN
topic Immunologic diseases. Allergy
RC581-607
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
spellingShingle 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
work_keys_str_mv AT christopherldmcmillan developmentofmolecularclampstabilizedhemagglutininvaccinesforinfluenzaaviruses
AT staceytmcheung developmentofmolecularclampstabilizedhemagglutininvaccinesforinfluenzaaviruses
AT naphakmodhiran developmentofmolecularclampstabilizedhemagglutininvaccinesforinfluenzaaviruses
AT jamesbarnes developmentofmolecularclampstabilizedhemagglutininvaccinesforinfluenzaaviruses
AT albertoaamarilla developmentofmolecularclampstabilizedhemagglutininvaccinesforinfluenzaaviruses
AT hellebielefeldtohmann developmentofmolecularclampstabilizedhemagglutininvaccinesforinfluenzaaviruses
AT leoyiyanglee developmentofmolecularclampstabilizedhemagglutininvaccinesforinfluenzaaviruses
AT kateguilfoyle developmentofmolecularclampstabilizedhemagglutininvaccinesforinfluenzaaviruses
AT geertvanamerongen developmentofmolecularclampstabilizedhemagglutininvaccinesforinfluenzaaviruses
AT koertstittelaar developmentofmolecularclampstabilizedhemagglutininvaccinesforinfluenzaaviruses
AT virginiejakon developmentofmolecularclampstabilizedhemagglutininvaccinesforinfluenzaaviruses
AT celialebas developmentofmolecularclampstabilizedhemagglutininvaccinesforinfluenzaaviruses
AT patrickreading developmentofmolecularclampstabilizedhemagglutininvaccinesforinfluenzaaviruses
AT kirstyrshort developmentofmolecularclampstabilizedhemagglutininvaccinesforinfluenzaaviruses
AT paulryoung developmentofmolecularclampstabilizedhemagglutininvaccinesforinfluenzaaviruses
AT danielwatterson developmentofmolecularclampstabilizedhemagglutininvaccinesforinfluenzaaviruses
AT keithjchappell developmentofmolecularclampstabilizedhemagglutininvaccinesforinfluenzaaviruses
_version_ 1718429432829444096