Development of a chimeric Zika vaccine using a licensed live-attenuated flavivirus vaccine as backbone

Xiao Feng Li; Hao Long Dong; Hong Jiang Wang; Xing Yao Huang; Ye Feng Qiu; Xue Ji; Qing Ye; Chunfeng Li; Yang Liu; Yong Qiang Deng; Tao Jiang; Gong Cheng; Fu Chun Zhang; Andrew D. Davidson; Ya Jun Song; Pei Yong Shi; Cheng Feng Qin

doi:10.1038/s41467-018-02975-w

Development of a chimeric Zika vaccine using a licensed live-attenuated flavivirus vaccine as backbone

Xiao Feng Li, Hao Long Dong, Hong Jiang Wang, Xing Yao Huang, Ye Feng Qiu, Xue Ji, Qing Ye, Chunfeng Li, Yang Liu, Yong Qiang Deng, Tao Jiang, Gong Cheng, Fu Chun Zhang, Andrew D. Davidson, Ya Jun Song, Pei Yong Shi, Cheng Feng Qin

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64 Scopus citations

Abstract

The global spread of Zika virus (ZIKV) and its unexpected association with congenital defects necessitates the rapid development of a safe and effective vaccine. Here we report the development and characterization of a recombinant chimeric ZIKV vaccine candidate (termed ChinZIKV) that expresses the prM-E proteins of ZIKV using the licensed Japanese encephalitis live-attenuated vaccine SA14-14-2 as the genetic backbone. ChinZIKV retains its replication activity and genetic stability in vitro, while exhibiting an attenuation phenotype in multiple animal models. Remarkably, immunization of mice and rhesus macaques with a single dose of ChinZIKV elicits robust and long-lasting immune responses, and confers complete protection against ZIKV challenge. Significantly, female mice immunized with ChinZIKV are protected against placental and fetal damage upon ZIKV challenge during pregnancy. Overall, our study provides an alternative vaccine platform in response to the ZIKV emergency, and the safety, immunogenicity, and protection profiles of ChinZIKV warrant further clinical development.

Original language	English (US)
Article number	673
Journal	Nature communications
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-02975-w
State	Published - Dec 1 2018
Externally published	Yes

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
General
Physics and Astronomy(all)

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Li, X. F., Dong, H. L., Wang, H. J., Huang, X. Y., Qiu, Y. F., Ji, X., Ye, Q., Li, C., Liu, Y., Deng, Y. Q., Jiang, T., Cheng, G., Zhang, F. C., Davidson, A. D., Song, Y. J., Shi, P. Y., & Qin, C. F. (2018). Development of a chimeric Zika vaccine using a licensed live-attenuated flavivirus vaccine as backbone. Nature communications, 9(1), [673]. https://doi.org/10.1038/s41467-018-02975-w

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title = "Development of a chimeric Zika vaccine using a licensed live-attenuated flavivirus vaccine as backbone",

abstract = "The global spread of Zika virus (ZIKV) and its unexpected association with congenital defects necessitates the rapid development of a safe and effective vaccine. Here we report the development and characterization of a recombinant chimeric ZIKV vaccine candidate (termed ChinZIKV) that expresses the prM-E proteins of ZIKV using the licensed Japanese encephalitis live-attenuated vaccine SA14-14-2 as the genetic backbone. ChinZIKV retains its replication activity and genetic stability in vitro, while exhibiting an attenuation phenotype in multiple animal models. Remarkably, immunization of mice and rhesus macaques with a single dose of ChinZIKV elicits robust and long-lasting immune responses, and confers complete protection against ZIKV challenge. Significantly, female mice immunized with ChinZIKV are protected against placental and fetal damage upon ZIKV challenge during pregnancy. Overall, our study provides an alternative vaccine platform in response to the ZIKV emergency, and the safety, immunogenicity, and protection profiles of ChinZIKV warrant further clinical development.",

author = "Li, {Xiao Feng} and Dong, {Hao Long} and Wang, {Hong Jiang} and Huang, {Xing Yao} and Qiu, {Ye Feng} and Xue Ji and Qing Ye and Chunfeng Li and Yang Liu and Deng, {Yong Qiang} and Tao Jiang and Gong Cheng and Zhang, {Fu Chun} and Davidson, {Andrew D.} and Song, {Ya Jun} and Shi, {Pei Yong} and Qin, {Cheng Feng}",

note = "Funding Information: We thank Dr. Bo Zhang (Wuhan Institute of Virology, CAS) and Professor Jing An (Capital Medical University) for critical reagents and insightful discussion. This work was supported by the National Natural Science Foundation of China (numbers 81661148054, 31770190, and 31470265), the National Science and Technology Major Project of China (numbers 2017ZX09101005, 2017ZX10304402, and 2017ZX10305501-003) and the Municipal Healthcare Joint-Innovation Major Project of Guangzhou (number 201704020229). C.F.Q. was supported by the NSFC Excellent Young Scientist Fund (number 81522025), Innovative Research Group (number 81621005), and Newton Advanced Fellowship from the UK Academy of Medical Sciences and the NSFC of China (number 81661130162). X.F.L. was supported by Beijing Nova Program (number 2016110). G.C. was supported by the National Key Research and Development Project of China (2016YFC1201000 and 2016ZX10004001-008). Publisher Copyright: {\textcopyright} 2018 The Author(s).",

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doi = "10.1038/s41467-018-02975-w",

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AU - Li, Xiao Feng

AU - Dong, Hao Long

AU - Wang, Hong Jiang

AU - Huang, Xing Yao

AU - Qiu, Ye Feng

AU - Ji, Xue

AU - Ye, Qing

AU - Li, Chunfeng

AU - Liu, Yang

AU - Deng, Yong Qiang

AU - Jiang, Tao

AU - Cheng, Gong

AU - Zhang, Fu Chun

AU - Davidson, Andrew D.

AU - Song, Ya Jun

AU - Shi, Pei Yong

AU - Qin, Cheng Feng

N1 - Funding Information: We thank Dr. Bo Zhang (Wuhan Institute of Virology, CAS) and Professor Jing An (Capital Medical University) for critical reagents and insightful discussion. This work was supported by the National Natural Science Foundation of China (numbers 81661148054, 31770190, and 31470265), the National Science and Technology Major Project of China (numbers 2017ZX09101005, 2017ZX10304402, and 2017ZX10305501-003) and the Municipal Healthcare Joint-Innovation Major Project of Guangzhou (number 201704020229). C.F.Q. was supported by the NSFC Excellent Young Scientist Fund (number 81522025), Innovative Research Group (number 81621005), and Newton Advanced Fellowship from the UK Academy of Medical Sciences and the NSFC of China (number 81661130162). X.F.L. was supported by Beijing Nova Program (number 2016110). G.C. was supported by the National Key Research and Development Project of China (2016YFC1201000 and 2016ZX10004001-008). Publisher Copyright: © 2018 The Author(s).

PY - 2018/12/1

Y1 - 2018/12/1

N2 - The global spread of Zika virus (ZIKV) and its unexpected association with congenital defects necessitates the rapid development of a safe and effective vaccine. Here we report the development and characterization of a recombinant chimeric ZIKV vaccine candidate (termed ChinZIKV) that expresses the prM-E proteins of ZIKV using the licensed Japanese encephalitis live-attenuated vaccine SA14-14-2 as the genetic backbone. ChinZIKV retains its replication activity and genetic stability in vitro, while exhibiting an attenuation phenotype in multiple animal models. Remarkably, immunization of mice and rhesus macaques with a single dose of ChinZIKV elicits robust and long-lasting immune responses, and confers complete protection against ZIKV challenge. Significantly, female mice immunized with ChinZIKV are protected against placental and fetal damage upon ZIKV challenge during pregnancy. Overall, our study provides an alternative vaccine platform in response to the ZIKV emergency, and the safety, immunogenicity, and protection profiles of ChinZIKV warrant further clinical development.

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Development of a chimeric Zika vaccine using a licensed live-attenuated flavivirus vaccine as backbone

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