Zhou Dan, Cheng Rao, Yao Yanfeng, Zhang Gan, Li Xin, Wang Bingjie, Wang Yong, Yu Feiyang, Yang Shangyu, Liu Hang, Gao Ge, Peng Yun, Chen Miaoyu, Deng Zengqin, Zhao Haiyan
State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei, China.
Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China.
NPJ Vaccines. 2024 Aug 31;9(1):158. doi: 10.1038/s41541-024-00954-5.
Nipah virus (NiV) is a zoonotic emergent paramyxovirus that can cause severe encephalitis and respiratory infections in humans, with a high fatality rate ranging from 40% to 75%. Currently, there are no approved human vaccines or antiviral drugs against NiV. Here, we designed a ferritin-based self-assembling nanoparticle displaying the NiV G head domain on the surface (NiV G-ferritin) and assessed immune responses elicited by the soluble NiV G head domain (NiV sG) or NiV G-ferritin. Immunization with NiV G-ferritin or NiV sG conferred complete protection against lethal NiV challenge without detection of viral RNA in Syrian golden hamsters. Compared to NiV sG, NiV G-ferritin induced significantly faster, broader, and higher serum neutralizing responses against three pathogenic henipaviruses (NiV-Malaysia, NiV-Bangladesh, and Hendra virus). Moreover, NiV G-ferritin induced a durable neutralizing immunity in mice as antisera potently inhibited NiV infection even after six months of the third immunization. Additionally, we isolated a panel of 27 NiV G-binding monoclonal antibodies (mAbs) from NiV G-ferritin immunized mice and found that these mAbs targeted four distinct antigenic sites on NiV G head domain with two sites that have not been defined previously. Notably, 25 isolated mAbs have potent neutralizing activity with 50% inhibitory concentrations less than 10 ng/mL against NiV pseudovirus. Collectively, these findings provide new insights into the immunogenicity of NiV G protein and reveal that NiV G-ferritin is a safe and highly effective vaccine candidate against Nipah virus infection.
尼帕病毒（NiV）是一种人畜共患的新兴副粘病毒，可导致人类严重脑炎和呼吸道感染，病死率高达40%至75%。目前，尚无获批的针对NiV的人用疫苗或抗病毒药物。在此，我们设计了一种基于铁蛋白的自组装纳米颗粒，其表面展示NiV G头部结构域（NiV G-铁蛋白），并评估了可溶性NiV G头部结构域（NiV sG）或NiV G-铁蛋白引发的免疫反应。用NiV G-铁蛋白或NiV sG免疫可使叙利亚金黄地鼠对致死性NiV攻击产生完全保护，且未检测到病毒RNA。与NiV sG相比，NiV G-铁蛋白诱导针对三种致病性亨尼帕病毒（马来西亚NiV、孟加拉国NiV和亨德拉病毒）的血清中和反应显著更快、更广且更高。此外，NiV G-铁蛋白在小鼠中诱导了持久的中和免疫力，因为即使在第三次免疫六个月后，抗血清仍能有效抑制NiV感染。此外，我们从经NiV G-铁蛋白免疫的小鼠中分离出一组27种NiV G结合单克隆抗体（mAb），发现这些mAb靶向NiV G头部结构域上四个不同的抗原位点，其中两个位点此前未被定义。值得注意的是，25种分离出的mAb具有强大的中和活性，对NiV假病毒的50%抑制浓度小于10 ng/mL。总体而言，这些发现为NiV G蛋白的免疫原性提供了新见解，并揭示NiV G-铁蛋白是一种安全且高效的抗尼帕病毒感染疫苗候选物。
