Shanghai Public Health Clinical Center, Fudan University, Shanghai, China; Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
Vaccine. 2021 Feb 5;39(6):915-925. doi: 10.1016/j.vaccine.2020.12.077. Epub 2021 Jan 13.
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.
寨卡病毒（ZIKV）感染最近引起了重大的公共卫生问题。为了开发寨卡病毒的亚单位疫苗，我们之前构建了重组寨卡病毒包膜蛋白结构域 III（EDIII）和整个外域（E80，包括 EDI、EDII 和 EDIII）作为候选疫苗，并在鼠模型中显示它们都具有免疫原性和保护作用。在这项后续研究中，我们在非人类灵长类动物中比较了这些候选疫苗。它们都能引起中和抗体反应，但只有 E80 免疫能抑制外周血和猴组织中的寨卡病毒感染，而 EDIII 可能通过抗体依赖性增强作用增加血液中的寨卡病毒 RNA。进一步的研究表明，E80 免疫的猴子中的病毒结合抗体反应持续时间更长、强度更高。这些结果表明，E80 作为候选疫苗优于 EDIII，并且病毒结合中和抗体的数量、质量和持久性与保护作用相关。
