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An mRNA vaccine against monkeypox virus inhibits infection by co-activation of humoral and cellular immune responses

Author

Listed:
  • Wanbo Tai

    (Shenzhen Bay Laboratory)

  • Chongyu Tian

    (Shenzhen Bay Laboratory
    Tsinghua University)

  • Huicheng Shi

    (Tsinghua University
    Nanjing Tech University)

  • Benjie Chai

    (Tsinghua University)

  • Xinyang Yu

    (Tsinghua University)

  • Xinyu Zhuang

    (Chinese Academy of Agricultural Sciences)

  • Pengyuan Dong

    (Shenzhen Bay Laboratory)

  • Min Li

    (Academy of Military Medical Sciences)

  • Qi Yin

    (Academy of Military Medical Sciences)

  • Shengyong Feng

    (Tsinghua University)

  • Weixiao Wang

    (Shenzhen Bay Laboratory)

  • Oujia Zhang

    (Tsinghua University)

  • Shibo Liang

    (Shenzhen Bay Laboratory)

  • Yang Liu

    (Shenzhen Bay Laboratory)

  • Jianying Liu

    (Shenzhen Bay Laboratory)

  • Longchao Zhu

    (Shenzhen Bay Laboratory)

  • Guangyu Zhao

    (Academy of Military Medical Sciences)

  • Mingyao Tian

    (Chinese Academy of Agricultural Sciences)

  • Guocan Yu

    (Tsinghua University)

  • Gong Cheng

    (Tsinghua University
    Shenzhen Center for Disease Control and Prevention
    Southwest United Graduate School)

Abstract

The persistent monkeypox outbreaks intensify the demand for monkeypox vaccines. Based on the mRNA vaccine platform, we conduct a systematic screening of monkeypox virus (MPXV) surface proteins from two types of viral particles, extracellular enveloped viruses (EVs) and intracellular mature viruses (MVs). This screening unveils 12 important antigens with diverse levels of neutralizing immunogenicity. Further assessment reveals that the combinations of 4, 8, and 12 of these antigens, namely Mix-4, Mix-8, and Mix-12, induce varying degrees of immune protection, with Mix-12 being the most potent. This finding demonstrates the significance of not only the level but also the diversity of the neutralizing antibodies in providing potent immune protection. Additionally, we utilize a T cell-epitope enrichment strategy, analyzing the complete proteome sequence of the MPXV to predict antigenic epitope-rich regions. Integration of these epitope-rich regions into a cellular immune-targeting antigen, named MPX-EPs, showcases that a cellular immune-targeting mRNA vaccine can independently confer immune protection. Furthermore, co-immunization with Mix-12 and MPX-EPs achieves complete protection against MPXV challenge. Overall, these results suggest an effective approach to enhance the immune protection of mRNA vaccines through the specific coordination of humoral and cellular immune responses.

Suggested Citation

  • Wanbo Tai & Chongyu Tian & Huicheng Shi & Benjie Chai & Xinyang Yu & Xinyu Zhuang & Pengyuan Dong & Min Li & Qi Yin & Shengyong Feng & Weixiao Wang & Oujia Zhang & Shibo Liang & Yang Liu & Jianying Li, 2025. "An mRNA vaccine against monkeypox virus inhibits infection by co-activation of humoral and cellular immune responses," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58328-x
    DOI: 10.1038/s41467-025-58328-x
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