Two immunogenic recombinant protein vaccine candidates showed disparate protective efficacy against Zika virus infection in rhesus macaques |
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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 |
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Affiliation: | 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 |
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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. |
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Keywords: | Zika virus EDIII E80 Vaccine Non-human primate Antibody-dependent enhancement |
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