-

nihao guest [ sign in / register ]
2026-3-5 7:46:02


Wang P, Li L, Chen Y, Tong L, Li Z, Yu R, Shen Q,. Attenuation of Influenza A Virus into Live Vaccines Through C-End Degrons. Adv Sci (Weinh). 2026 Feb 21:e09425
submited by kickingbird at Feb, 22, 2026 13:44 PM from Adv Sci (Weinh). 2026 Feb 21:e09425

Harnessing the cell´s ubiquitin-proteasome system (UPS) to manipulate viral protein degradation represents a promising way to develop live attenuated vaccines. We previously developed a proteolysis-targeting (PROTAR) vaccine technology by artificially fusing a proteasome-targeting degron (PTD) to the C terminus of influenza A viral M1 protein. Given the requirement of the PROTAR vaccine technology for PTD to be placed at the C terminus of viral proteins, we assumed that this technology could be generalized to the naturally occurring C-end degrons. To explore this, we generated PROTAR vaccine strains by individually incorporating three C-end degrons at the C terminus of influenza viral M1 protein. All generated PROTAR vaccine strains, namely M1C-degron-1, M1C-degron-2, and M1C-degron-3, exhibited proteasome-dependent viral M1 protein degradation and robust attenuation in conventional host cells, while maintaining efficient replication in engineered TEVp-expressing cells suitable for large-scale manufacturing. These vaccine strains also showed sufficient attenuation and safety in vivo. A single intranasal dose elicited potent humoral, mucosal, and markedly enhanced T cell immune responses, supported by PTD-mediated increases in M1 antigen presentation. Importantly, the vaccines conferred strong protection against both homologous H1N1 and heterologous H3N2 infection, with heterologous immunity shown to be CD8+ T cell-dependent rather than antibody-mediated. This study demonstrates the general applicability of natural C-end degrons in PROTAR vaccine design, expanding the scope and versatility of PROTAR live attenuated vaccine technology.

See Also:

Latest articles in those days:

[Go Top]    [Close Window]

Related Pages:
Learn about the flu news, articles, events and more
Subscribe to the weekly F.I.C newsletter!


  

Site map  |   Contact us  |  Term of use  |  FAQs |  粤ICP备10094839号-1
Copyright ©www.flu.org.cn. 2004-2026. All Rights Reserved. Powered by FIC 4.0.1
  Email:webmaster@flu.org.cn