Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Tools of the Trade
  • Published:

Live vaccine development through targeted protein degradation

Nature Reviews Immunology volume 25, page 633 (2025)Cite this article

Subjects

Access through your institution
Buy or subscribe

Vaccination is one of the most effective ways to protect populations from viral infections. A popular method for vaccine development involves attenuating viruses to weaken their ability to cause disease for use as live vaccines. Live attenuated vaccines work well as they preserve all viral antigens in their native conformations, elicit strong mucosal, humoral and cellular immune responses, and can be administered without needles. However, finding the balance between safety and immunogenicity remains a major ongoing challenge for live attenuated vaccine development: over-attenuation may reduce immunogenicity, whereas insufficient attenuation can compromise safety. To work towards addressing this challenge, we developed a proteolysis-targeting (PROTAR) live attenuated vaccine strategy using influenza virus as a model system. This strategy attenuates virulent viruses into safe live vaccines while increasing viral antigen presentation for enhanced immune responses.

“This strategy attenuates virulent viruses into safe live vaccines while increasing viral antigen presentation for enhanced immune responses”

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

Related articles

Download references

Author information

Authors and Affiliations

  1. State Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China

    Qisi Zhang & Longlong Si

  2. University of Chinese Academy of Sciences, Beijing, China

    Longlong Si

Authors
  1. Qisi Zhang
    View author publications

    Search author on:PubMed Google Scholar

  2. Longlong Si
    View author publications

    Search author on:PubMed Google Scholar

Corresponding author

Correspondence to Longlong Si.

Ethics declarations

Competing interests

L.S. is an inventor on patent applications describing the PROTAR vaccine technologies. Q.Z. declares no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, Q., Si, L. Live vaccine development through targeted protein degradation. Nat Rev Immunol 25, 633 (2025). https://doi.org/10.1038/s41577-025-01212-y

Download citation

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41577-025-01212-y

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing