Nature Reviews Immunology, Published online: 24 July 2025; doi:10.1038/s41577-025-01212-y

In this Tools of the Trade article, Qisi Zhang and Longlong Si describe a method for generating live attenuated vaccines that involves targeting viruses to the host cells’ protein degradation machinery, which attenuates the virus within the host and also enhances viral antigen presentation.



Summary

Zhang and Si present a novel method for live attenuated vaccine development in Nature Reviews Immunology. Their approach utilizes the host cell’s protein degradation machinery to weaken viruses. By targeting viruses to these degradation pathways, the virus’s ability to replicate and cause disease is reduced within the host. Simultaneously, this process boosts the presentation of viral antigens, potentially leading to a stronger and more effective immune response. This technique offers a promising new avenue for creating safer and more immunogenic live attenuated vaccines.

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