tetano
Editor, Senior Moderator
NPJ Vaccines
. 2021 Nov 8;6(1):135.
doi: 10.1038/s41541-021-00395-4.
Development of molecular clamp stabilized hemagglutinin vaccines for Influenza A viruses
Christopher L D McMillan[SUP] 1 [/SUP], Stacey T M Cheung[SUP] 2 [/SUP], Naphak Modhiran[SUP] 2 [/SUP], James Barnes[SUP] 3 [/SUP], Alberto A Amarilla[SUP] 2 [/SUP], Helle Bielefeldt-Ohmann[SUP] 2 4 5 [/SUP], Leo Yi Yang Lee[SUP] 3 [/SUP], Kate Guilfoyle[SUP] 6 [/SUP], Geert van Amerongen[SUP] 6 [/SUP], Koert Stittelaar[SUP] 6 [/SUP], Virginie Jakon[SUP] 7 [/SUP], Celia Lebas[SUP] 7 [/SUP], Patrick Reading[SUP] 3 8 [/SUP], Kirsty R Short[SUP] 2 4 [/SUP], Paul R Young[SUP] 9 10 11 [/SUP], Daniel Watterson[SUP] 12 13 14 [/SUP], Keith J Chappell[SUP] 15 16 17 [/SUP]
Affiliations
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.
. 2021 Nov 8;6(1):135.
doi: 10.1038/s41541-021-00395-4.
Development of molecular clamp stabilized hemagglutinin vaccines for Influenza A viruses
Christopher L D McMillan[SUP] 1 [/SUP], Stacey T M Cheung[SUP] 2 [/SUP], Naphak Modhiran[SUP] 2 [/SUP], James Barnes[SUP] 3 [/SUP], Alberto A Amarilla[SUP] 2 [/SUP], Helle Bielefeldt-Ohmann[SUP] 2 4 5 [/SUP], Leo Yi Yang Lee[SUP] 3 [/SUP], Kate Guilfoyle[SUP] 6 [/SUP], Geert van Amerongen[SUP] 6 [/SUP], Koert Stittelaar[SUP] 6 [/SUP], Virginie Jakon[SUP] 7 [/SUP], Celia Lebas[SUP] 7 [/SUP], Patrick Reading[SUP] 3 8 [/SUP], Kirsty R Short[SUP] 2 4 [/SUP], Paul R Young[SUP] 9 10 11 [/SUP], Daniel Watterson[SUP] 12 13 14 [/SUP], Keith J Chappell[SUP] 15 16 17 [/SUP]
Affiliations
- PMID: 34750396
- DOI: 10.1038/s41541-021-00395-4
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.