Harnessing chaperone-mediated autophagy for the development of live attenuated influenza vaccines

Targeted degradation of viral proteins has emerged as a powerful strategy to attenuate virulent viruses into live vaccines. In our recent study, we introduced a lysosome-targeting (LYTAR) live attenuated vaccine platform that utilizes chaperone-mediated autophagy (CMA), a lysosome-dependent degradation pathway, to conditionally degrade viral proteins and convert virulent influenza A viruses into safe and effective live attenuated vaccines. The LYTAR vaccine approach enables controlled attenuation of viral replication, while preserving the full antigenic composition of the virus and maintaining robust immunogenicity.