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Development of a skin- and neuro-attenuated live vaccine for varicella

Author

Listed:
  • Wei Wang

    (Xiamen University)

  • Dequan Pan

    (Xiamen University)

  • Wenkun Fu

    (Xiamen University)

  • Xiangzhong Ye

    (Beijing Wantai Biological Pharmacy Enterprise Co., Ltd.)

  • Jinle Han

    (Beijing Wantai Biological Pharmacy Enterprise Co., Ltd.)

  • Lianwei Yang

    (Beijing Wantai Biological Pharmacy Enterprise Co., Ltd.)

  • Jizong Jia

    (Beijing Wantai Biological Pharmacy Enterprise Co., Ltd.)

  • Jian Liu

    (Xiamen University)

  • Rui Zhu

    (Xiamen University)

  • Yali Zhang

    (Xiamen University)

  • Che Liu

    (Xiamen University)

  • Jianghui Ye

    (Xiamen University)

  • Anca Selariu

    (Rutgers University)

  • Yuqiong Que

    (Xiamen University)

  • Qinjian Zhao

    (Xiamen University)

  • Ting Wu

    (Xiamen University)

  • Yimin Li

    (Beijing Wantai Biological Pharmacy Enterprise Co., Ltd.)

  • Jun Zhang

    (Xiamen University)

  • Tong Cheng

    (Xiamen University)

  • Hua Zhu

    (Rutgers University)

  • Ningshao Xia

    (Xiamen University)

Abstract

Varicella caused by the primary infection of varicella-zoster virus (VZV) exerts a considerable disease burden globally. Current varicella vaccines consisting of the live-attenuated vOka strain of VZV are generally safe and effective. However, vOka retains full neurovirulence and can establish latency and reactivate to cause herpes zoster in vaccine recipients, raising safety concerns. Here, we rationally design a live-attenuated varicella vaccine candidate, v7D. This virus replicates like wild-type virus in MRC-5 fibroblasts and human PBMCs, the carrier for VZV dissemination, but is severely impaired for infection of human skin and neuronal cells. Meanwhile, v7D shows immunogenicity comparable to vOka both in vitro and in multiple small animal species. Finally, v7D is proven well-tolerated and immunogenic in nonhuman primates. Our preclinical data suggest that v7D is a promising candidate as a safer live varicella vaccine with reduced risk of vaccine-related complications, and could inform the design of other herpes virus vaccines.

Suggested Citation

  • Wei Wang & Dequan Pan & Wenkun Fu & Xiangzhong Ye & Jinle Han & Lianwei Yang & Jizong Jia & Jian Liu & Rui Zhu & Yali Zhang & Che Liu & Jianghui Ye & Anca Selariu & Yuqiong Que & Qinjian Zhao & Ting W, 2022. "Development of a skin- and neuro-attenuated live vaccine for varicella," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28329-1
    DOI: 10.1038/s41467-022-28329-1
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    References listed on IDEAS

    as
    1. Daniel P. Depledge & Werner J. D. Ouwendijk & Tomohiko Sadaoka & Shirley E. Braspenning & Yasuko Mori & Randall J. Cohrs & Georges M. G. M. Verjans & Judith Breuer, 2018. "A spliced latency-associated VZV transcript maps antisense to the viral transactivator gene 61," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
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