寨卡病毒(ZIKV)可诱导神经系统和自身免疫性并发症,例如小头畸形和格林-巴利综合征。有效的疫苗是预防ZIKV感染所必需的。ZIKV的E蛋白负责病毒的附着,条目,和融合。E蛋白的结构域III(EDIII)含有中和表位,是ZIKV疫苗抗原的理想选择。然而,EDIII免疫原性差。CRM197是一种载体蛋白,可以激活EDIII的T辅助细胞。甘露聚糖是TLR-4或TLR-2的配体。八臂PEG可以在一个实体中连接多个EDIII分子。在本研究中,EDIII与CRM197、8臂PEG和甘露聚糖共价缀合以提高EDIII的免疫原性。缀合物(CRM-EDIII-PM)在BALB/c小鼠中引发高EDIII特异性抗体滴度。Th1型细胞因子(IFN-γ和IL-2)和Th2型细胞因子(IL-5和IL-10)以显著水平分泌。因此,CRM-EDIII-PM可以刺激对EDIII的有效体液和细胞免疫反应。CRM-EDIII-PM对免疫系统的血清暴露时间延长。此外,CRM-EDIII-PM未导致对器官的明显毒性。因此,CRM-EDIII-PM因其诱导强免疫应答的能力而被预期为有希望的疫苗候选物。
Zika virus (ZIKV) induces neurological and autoimmune complications such as microcephaly and Guillain-Barre syndrome. Effective vaccines are necessary to prevent the ZIKV infection. E protein of ZIKV is responsible for virus attachment, entry, and fusion. The domain III of E protein (EDIII) contains the neutralizing epitopes and is ideal to act as an antigen for ZIKV vaccine. However,
EDIII is poorly immunogenic. CRM197 is a carrier protein and can activate T helper cells for EDIII. Mannan is a ligand of TLR-4 or TLR-2. Eight-arm PEG can link multiple
EDIII molecules in one entity. In the present study, EDIII was covalently conjugated with CRM197, 8-arm PEG and mannan to improve the immunogenicity of
EDIII. The conjugate (CRM-
EDIII-PM) elicited high
EDIII-specific antibody titers in the BALB/c mice. Th1-type cytokines (IFN-γ and IL-2) and Th2-type cytokines (IL-5 and IL-10) were secreted at a marked level. Thus, CRM-
EDIII-PM could stimulate potent humoral and cellular immune response to
EDIII. The serum exposure of CRM-EDIII-PM to the immune system was prolonged. Moreover, CRM-EDIII-PM did not lead to apparent toxicity to the organs. Therefore, CRM-EDIII-PM was expected as a promising vaccine candidate for its ability to induce strong immune responses.