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昆虫细胞中产生的马尔堡病毒样颗粒可诱导恒河猴产生中和抗体。

Marburg virus-like particles produced in insect cells induce neutralizing antibodies in rhesus macaques.

机构信息

College of Veterinary Medicine, Jilin University, Changchun, China.

Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun, China.

出版信息

J Med Virol. 2017 Dec;89(12):2069-2074. doi: 10.1002/jmv.24832. Epub 2017 Sep 1.

Abstract

Marburg virus (MARV), which is one of the most virulent agents in the world, causes lethal haemorrhagic fever in humans and nonhuman primates (NHPs) with a mortality rate of up to 90%. Currently, there is no effective treatment or approved vaccine for MARV for human use to control disease outbreak and spread. Virus-like particles (VLPs), which are morphologically identical to the native infectious virus particle, are efficacious as vaccines against many viruses, including human papilloma virus (HPV), porcine circovirus (PCV) type 2 and hepatitis B virus (HBV). In this study, we generated MARV virus-like particles (VLPs) by co-expressing a glycoprotein (GP) and matrix protein (VP40) using the baculovirus expression system. Rhesus macaques vaccinated with MARV VLPs mixed with adjuvant Poria cocos polysaccharides (PCP-II) produced a GP-specific IgG titer of up to 1:1280 and virus-neutralizing antibody titers that reached 1:320. MARV VLPs also elicited interferon-γ (IFN-γ) and interleukin-4 (IL-4) secretion associated with T-helper 1 cell (Th1)- and T-helper 2 cell (Th2)-mediated immunity, as detected using enzyme-linked immunospot (ELISpot) assays. These data indicate that MARV VLPs mixed with adjuvant PCP-II have excellent immunogenicity in rhesus macaques and may be a promising candidate vaccine against MARV.

摘要

马尔堡病毒(MARV)是世界上最具毒性的病原体之一,可导致人类和非人灵长类动物(NHPs)发生致命性出血热,死亡率高达 90%。目前,尚无针对 MARV 的有效治疗方法或经批准的人类用疫苗来控制疾病爆发和传播。病毒样颗粒(VLPs)在形态上与天然感染性病毒颗粒相同,是针对许多病毒(包括人乳头瘤病毒(HPV)、猪圆环病毒 2 型(PCV 2)和乙型肝炎病毒(HBV))的有效疫苗。在这项研究中,我们通过使用杆状病毒表达系统共表达糖蛋白(GP)和基质蛋白(VP40)来产生 MARV 病毒样颗粒(VLPs)。用 MARV VLPs 与佐剂茯苓多糖(PCP-II)混合接种的恒河猴产生的 GP 特异性 IgG 滴度高达 1:1280,中和抗体滴度达到 1:320。MARV VLPs 还引发了与 T 辅助 1 细胞(Th1)和 T 辅助 2 细胞(Th2)介导的免疫相关的干扰素-γ(IFN-γ)和白细胞介素-4(IL-4)分泌,这是通过酶联免疫斑点(ELISpot)检测到的。这些数据表明,与佐剂 PCP-II 混合的 MARV VLPs 在恒河猴中具有优异的免疫原性,可能是一种有前途的 MARV 候选疫苗。

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