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

Biochemistry & Molecular Biology

Research output: Contribution to journal › Article › peer-review

79 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

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

Access to Document

10.1038/s41467-018-02975-w

Cite this

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), Article 673. https://doi.org/10.1038/s41467-018-02975-w

@article{1eab5d3c255047b0b271fd77cc56b7d9,

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 = "Publisher Copyright: {\textcopyright} 2018 The Author(s).",

year = "2018",

month = dec,

day = "1",

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

language = "English (US)",

volume = "9",

journal = "Nature communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

T1 - Development of a chimeric Zika vaccine using a licensed live-attenuated flavivirus vaccine as backbone

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

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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85042071353&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85042071353&partnerID=8YFLogxK

U2 - 10.1038/s41467-018-02975-w

DO - 10.1038/s41467-018-02975-w

M3 - Article

C2 - 29445153

AN - SCOPUS:85042071353

SN - 2041-1723

VL - 9

JO - Nature communications

JF - Nature communications

IS - 1

M1 - 673

ER -

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

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this