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Two immunogenic recombinant protein vaccine candidates showed disparate protective efficacy against Zika virus infection in rhesus macaques
Authors:Ruoheng Yang  Qingwei Liu  Wei Pang  Fei Gao  Huabin Liang  Wei Zhang  Yalong Lin  Min Li  Zhihua Liu  George F Gao  Linqi Zhang  Hui Xiao  Yongtang Zheng  Zhong Huang  Xia Jin
Institution:1. Shanghai Public Health Clinical Center, Fudan University, Shanghai, China;2. Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China;3. Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China;4. Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China;5. Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
Abstract:Zika virus (ZIKV) infection has caused major public health problems recently. To develop subunit vaccines for ZIKV, we have previously constructed recombinant ZIKV envelope protein domain III (EDIII), and the entire ectodomain (E80, which comprises EDI, EDII and EDIII), as vaccine candidates and showed both of them being immunogenic and protective in murine models. In this follow-up study, we compared these vaccine candidates in non-human primates. Both of them elicited neutralizing antibody responses, but only E80 immunization inhibited ZIKV infection in both peripheral blood and monkey tissues, whereas EDIII increased blood ZIKV RNA through possibly antibody-dependent enhancement. Further investigations revealed that the virion-binding antibody response in E80 immunized monkeys persisted longer and stronger than in EDIII immunized monkeys. These results demonstrate that E80 is superior to EDIII as a vaccine candidate, and that the magnitude, quality and durability of virion-binding neutralizing antibodies are correlates of protection.
Keywords:Zika virus  EDIII  E80  Vaccine  Non-human primate  Antibody-dependent enhancement
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