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

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 Wu, Yimin Li, Jun Zhang (), Tong Cheng (), Hua Zhu () and Ningshao Xia ()
Additional contact information
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

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-28329-1

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