Abstract：
Zika virus (ZIKV) infection remains a global public health problem. After the \"Public Health Emergencies of International Concern\" declared in February 2016, the incidence of new infections by this pathogen has been decreasing in many areas. However, there is still a likely risk that ZIKV will spread to more countries. To date, there is no vaccine or antiviral drug available to prevent or treat Zika virus infection. In the Zika vaccine development, those based on protein subunits are attractive as a non-replicable platform due to their potentially enhanced safety profile to be used in all populations. However, these vaccines frequently require multiple doses and adjuvants to achieve protective immunity. In this study we show the immunological evaluation of new formulations of the recombinant protein ZEC, which combines regions of domain III of the envelope and the capsid from ZIKV. Two nucleotide-based adjuvants were used to enhance the immunity elicited by the vaccine candidate ZEC. ODN 39M or c-di-AMP was incorporated as immunomodulator into the formulations combined with aluminum hydroxide. Following immunizations in immunocompetent BALB/c mice, the formulations stimulated high IgG antibodies. Although the IgG subtypes suggested a predominantly Th1-biased immune response by the formulation including the ODN 39M, cellular immune responses measured by IFNγ secretion from spleen cells after in vitro stimulations were induced by both immunomodulators. These results demonstrate the capacity of both immunomodulators to enhance the immunogenicity of the recombinant subunit ZEC as a vaccine candidate against ZIKV.
摘要：
寨卡病毒（ZIKV）感染仍然是一个全球性的公共卫生问题。在2016年2月宣布“国际关注的突发公共卫生事件”之后，该病原体在许多地区的新感染发病率一直在下降。然而,ZIKV仍有可能传播到更多国家的风险。迄今为止,目前尚无疫苗或抗病毒药物可用于预防或治疗寨卡病毒感染。在寨卡疫苗开发中，那些基于蛋白质亚基的细胞作为不可复制的平台是有吸引力的,因为它们具有潜在的增强的安全性,可以在所有人群中使用.然而,这些疫苗通常需要多剂量和佐剂来实现保护性免疫。在这项研究中，我们展示了重组蛋白ZEC的新制剂的免疫学评估，它结合了包膜的结构域III的区域和来自ZIKV的衣壳。使用两种基于核苷酸的佐剂来增强由疫苗候选物ZEC引起的免疫。将ODN39M或c-di-AMP作为免疫调节剂掺入与氢氧化铝组合的制剂中。在免疫活性BALB/c小鼠中进行免疫接种后，该制剂刺激高IgG抗体。尽管IgG亚型表明包含ODN39M的制剂主要有Th1偏向性免疫应答，通过两种免疫调节剂诱导体外刺激后从脾细胞分泌IFNγ测量的细胞免疫应答。这些结果证明了两种免疫调节剂增强重组亚基ZEC作为针对ZIKV的疫苗候选物的免疫原性的能力。
