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.

• Authors: 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
• Journal: Nature communications (Nat Commun) Vol. 9 Issue 1 Pg. 673 (02 14 2018) ISSN: 2041-1723 [Electronic] England
• PMID: 29445153 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Neutralizing
• Antibodies, Viral
• Vaccines, Attenuated
• Vaccines, Synthetic
• Viral Vaccines

Topics

• Aedes (virology)
• Animals
• Antibodies, Neutralizing (biosynthesis)
• Antibodies, Viral (biosynthesis)
• Disease Models, Animal
• Encephalitis Virus, Japanese (genetics, immunology)
• Female
• Genetic Engineering
• Humans
• Infectious Disease Transmission, Vertical (prevention & control)
• Macaca mulatta
• Male
• Mice
• Mice, 129 Strain
• Mice, Inbred BALB C
• Mosquito Vectors (virology)
• Pregnancy
• Vaccines, Attenuated (adverse effects, genetics, immunology)
• Vaccines, Synthetic (adverse effects, genetics, immunology)
• Viral Vaccines (adverse effects, genetics, immunology)
• Viremia (prevention & control)
• Zika Virus (genetics, immunology)
• Zika Virus Infection (immunology, prevention & control, virology)