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
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:
- Birth cohort effects in adults associated with influenza A(H1N1)pdm09 vaccine effectiveness 12 hours ago
- Genetic Characterization of Swine Influenza Viruses in Thailand in 2019-2025 Reveals Novel Reassortants 12 hours ago
- Outbreak dynamics of high pathogenicity avian influenza virus H5N1, clade 2.3.4.4b euBB, in black-headed gulls and common terns in Germany in 2023 13 hours ago
- [preprint]The canine respiratory epithelium is a permissive ecosystem for influenza interspecies transmission and emergence 13 hours ago
- [preprint]Explainable and Calibrated AI for Decoding Host-Adaptive Changes in Influenza A Virus 13 hours ago
[Go Top] [Close Window]


