National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan.
Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.
J Biomed Sci. 2020 Apr 14;27(1):51. doi: 10.1186/s12929-020-00646-x.
The emergence of Zika virus (ZV) in tropical and subtropical areas of the world has created an urgent need for vaccines against ZV. However, approved vaccines that prevent ZV infection are not available. To develop an effective vaccine against ZV infection, a lipidated form of ZV envelope protein domain III that possesses an intrinsic adjuvant property was rationally designed. Our goal was to examine the immunogenicity of recombinant lipidated ZV envelope protein domain III (rLZE3) and evaluate its potential as a vaccine candidate against ZV.
Recombinant ZV envelope protein domain III (rZE3) and rLZE3 were prepared with an Escherichia coli-based system. Dendritic cell surface marker expression and cytokine production upon stimulation were analyzed to evaluate the function of rLZE3. Neutralizing antibody capacities were evaluated using focus reduction neutralization tests after immunization. To investigate the protective immunity in immunized mice, serum samples collected from immunized mice were adoptively transferred into AG129 mice, and then viremia levels and survival times were examined after ZV challenge.
rLZE3 alone but not rZE3 alone efficiently activated dendritic cells in vitro and was taken up by dendritic cells in vivo. Immunization of C57BL/6 mice with rLZE3 alone (without exogenous adjuvant) could induce ZV-specific neutralizing antibody responses. Furthermore, serum samples obtained from rLZE3-immunized mice provided protection as indicated by a reduction in viremia levels and prolongation of survival times after ZV challenge.
These results indicate that rLZE3 is an excellent vaccine candidate and has great potential that should be evaluated in further preclinical studies.
寨卡病毒（ZV）在世界热带和亚热带地区的出现，迫切需要针对 ZV 的疫苗。然而，目前尚无预防 ZV 感染的批准疫苗。为了开发针对 ZV 感染的有效疫苗，我们合理设计了具有内在佐剂特性的 ZV 包膜蛋白结构域 III 的脂质化形式。我们的目标是研究重组 ZV 包膜蛋白结构域 III（rLZE3）的免疫原性，并评估其作为 ZV 候选疫苗的潜力。
使用基于大肠杆菌的系统制备重组 ZV 包膜蛋白结构域 III（rZE3）和 rLZE3。通过分析树突状细胞表面标志物的表达和细胞因子的产生来评估 rLZE3 的功能。通过免疫接种后进行焦点减少中和试验评估中和抗体能力。为了研究免疫接种小鼠的保护免疫力，从免疫接种小鼠收集的血清样本被过继转移到 AG129 小鼠中，然后在 ZV 攻击后检查病毒血症水平和存活时间。
单独的 rLZE3 而不是单独的 rZE3 能够有效地在体外激活树突状细胞，并在体内被树突状细胞摄取。单独用 rLZE3（无外源性佐剂）免疫 C57BL/6 小鼠可诱导 ZV 特异性中和抗体反应。此外，从 rLZE3 免疫接种的小鼠获得的血清样本提供了保护，表现为病毒血症水平降低和 ZV 攻击后存活时间延长。
这些结果表明 rLZE3 是一种优秀的疫苗候选物，具有巨大的潜力，应在进一步的临床前研究中进行评估。
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