Department of Microbiology, Center for Biodefense and Emerging Infectious Disease, University of Texas Medical Branch, Galveston, Texas, United States of America.
PLoS One. 2011 Apr 6;6(4):e18437. doi: 10.1371/journal.pone.0018437.
Nipah virus (NiV) was first recognized in 1998 in a zoonotic disease outbreak associated with highly lethal febrile encephalitis in humans and a predominantly respiratory disease in pigs. Periodic deadly outbreaks, documentation of person-to-person transmission, and the potential of this virus as an agent of agroterror reinforce the need for effective means of therapy and prevention. In this report, we describe the vaccine potential of NiV virus-like particles (NiV VLPs) composed of three NiV proteins G, F and M. Co-expression of these proteins under optimized conditions resulted in quantifiable amounts of VLPs with many virus-like/vaccine desirable properties including some not previously described for VLPs of any paramyxovirus: The particles were fusogenic, inducing syncytia formation; PCR array analysis showed NiV VLP-induced activation of innate immune defense pathways; the surface structure of NiV VLPs imaged by cryoelectron microscopy was dense, ordered, and repetitive, and consistent with similarly derived structure of paramyxovirus measles virus. The VLPs were composed of all the three viral proteins as designed, and their intracellular processing also appeared similar to NiV virions. The size, morphology and surface composition of the VLPs were consistent with the parental virus, and importantly, they retained their antigenic potential. Finally, these particles, formulated without adjuvant, were able to induce neutralizing antibody response in Balb/c mice. These findings indicate vaccine potential of these particles and will be the basis for undertaking future protective efficacy studies in animal models of NiV disease.
尼帕病毒（NiV）于 1998 年首次在与人类高度致命性发热性脑炎和猪主要呼吸道疾病相关的人畜共患疾病爆发中被发现。周期性的致命性爆发、人际传播的记录以及这种病毒作为农业恐怖主义手段的潜力，都加强了对有效治疗和预防手段的需求。在本报告中，我们描述了由尼帕病毒三种蛋白 G、F 和 M 组成的尼帕病毒样颗粒（NiV VLPs）的疫苗潜力。在优化条件下共表达这些蛋白会产生可量化的 VLPs，具有许多病毒样/疫苗所需的特性，其中一些特性以前从未在任何副粘病毒的 VLPs 中描述过：这些颗粒具有融合性，可诱导合胞体形成；PCR 数组分析显示 NiV VLP 诱导了先天免疫防御途径的激活；冷冻电子显微镜下观察到 NiV VLPs 的表面结构密集、有序且具有重复性，与类似来源的副粘病毒麻疹病毒的结构一致。VLPs 如设计的那样由三种病毒蛋白组成，其细胞内加工也似乎与 NiV 病毒粒子相似。VLPs 的大小、形态和表面组成与亲本病毒一致，重要的是，它们保留了其抗原性潜力。最后，这些颗粒在没有佐剂的情况下被制成制剂，能够在 Balb/c 小鼠中诱导中和抗体反应。这些发现表明这些颗粒具有疫苗潜力，并将成为在 NiV 疾病动物模型中进行未来保护效力研究的基础。
