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