TY - JOUR
T1 - Development of a skin- and neuro-attenuated live vaccine for varicella
AU - Wang, Wei
AU - Pan, Dequan
AU - Fu, Wenkun
AU - Ye, Xiangzhong
AU - Han, Jinle
AU - Yang, Lianwei
AU - Jia, Jizong
AU - Liu, Jian
AU - Zhu, Rui
AU - Zhang, Yali
AU - Liu, Che
AU - Ye, Jianghui
AU - Selariu, Anca
AU - Que, Yuqiong
AU - Zhao, Qinjian
AU - Wu, Ting
AU - Li, Yimin
AU - Zhang, Jun
AU - Cheng, Tong
AU - Zhu, Hua
AU - Xia, Ningshao
N1 - Funding Information:
This research was supported by grants from the National Natural Science Foundation of China (Nos. 81871648, 82171833, and 81601762), the National Science and Technology Major Projects for Major New Drugs Innovation and Development (No. 2018ZX09711003-005-003), and the National Science and Technology Major Project of Infectious Diseases (No. 2017ZX10304402). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-022-28329-1
DO - 10.1038/s41467-022-28329-1
M3 - Article
C2 - 35149692
AN - SCOPUS:85124576430
SN - 2041-1723
VL - 13
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 824
ER -