Kumar Kiven, Ong Hui Kian, Tan Wen Siang, Arshad Siti Suri, Ho Kok Lian
Department of Pathology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia (UPM), Serdang 43400, Selangor, Malaysia.
Department of Microbiology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia (UPM), Serdang 43400, Selangor, Malaysia.
Pharmaceutics. 2021 Nov 1;13(11):1826. doi: 10.3390/pharmaceutics13111826.
Japanese encephalitis virus (JEV) is the pathogen that causes Japanese encephalitis (JE) in humans and horses. Lethality of the virus was reported to be between 20-30%, of which, 30-50% of the JE survivors develop neurological and psychiatric sequelae. Attributed to the low effectiveness of current therapeutic approaches against JEV, vaccination remains the only effective approach to prevent the viral infection. Currently, live-attenuated and chimeric-live vaccines are widely used worldwide but these vaccines pose a risk of virulence restoration. Therefore, continuing development of JE vaccines with higher safety profiles and better protective efficacies is urgently needed. In this study, the nodavirus (NV) capsid protein (CP) fused with the domain III of JEV envelope protein (JEV-DIII) was produced in . The fusion protein (NV-CP) assembled into virus-like particles (VLPs) with a diameter of approximately 18 nm. The BALB/c mice injected with the VLPs alone or in the presence of alum successfully elicited the production of anti-JEV-DIII antibody, with titers significantly higher than that in mice immunized with IMOJEV, a commercially available vaccine. Immunophenotyping showed that the NV-CP supplemented with alum triggered proliferation of cytotoxic T-lymphocytes, macrophages, and natural killer (NK) cells. Additionally, cytokine profiles of the immunized mice revealed activities of cytotoxic T-lymphocytes, macrophages, and NK cells, indicating the activation of adaptive cellular and innate immune responses mediated by NV-CP VLPs. Induction of innate, humoral, and cellular immune responses by the NV-CP VLPs suggest that the chimeric protein is a promising JEV vaccine candidate.
日本脑炎病毒（JEV）是导致人类和马匹患日本脑炎（JE）的病原体。据报道，该病毒的致死率在20%至30%之间，其中，30%至50%的JE幸存者会出现神经和精神后遗症。由于目前针对JEV的治疗方法效果不佳，接种疫苗仍然是预防病毒感染的唯一有效方法。目前，减毒活疫苗和嵌合活疫苗在全球广泛使用，但这些疫苗存在毒力恢复的风险。因此，迫切需要继续研发具有更高安全性和更好保护效力的JE疫苗。在本研究中，在……中产生了与JEV包膜蛋白结构域III（JEV-DIII）融合的诺达病毒（NV）衣壳蛋白（CP）。融合蛋白（NV-CP）组装成直径约为18 nm的病毒样颗粒（VLP）。单独注射VLP或在明矾存在的情况下注射VLP的BALB/c小鼠成功诱导产生了抗JEV-DIII抗体，其滴度显著高于用市售疫苗IMOJEV免疫的小鼠。免疫表型分析表明，添加明矾的NV-CP可触发细胞毒性T淋巴细胞、巨噬细胞和自然杀伤（NK）细胞的增殖。此外，免疫小鼠的细胞因子谱揭示了细胞毒性T淋巴细胞、巨噬细胞和NK细胞的活性，表明NV-CP VLP介导的适应性细胞免疫反应和先天性免疫反应被激活。NV-CP VLP诱导的先天性、体液性和细胞免疫反应表明，这种嵌合蛋白是一种有前景的JEV疫苗候选物。
