Marburg virus-like particles produced in insect cells induce neutralizing antibodies in rhesus macaques
Marburg virus-like particles produced in insect cells induce neutralizing antibodies in rhesus macaques
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DOI：
10.1002/jmv.24832
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发表时间：
2017-12-01
影响因子：
12.7
通讯作者：
Xia Xianzhu
中科院分区：
文献类型：
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作者：
Gai Weiwei;Zheng Xuexing;Xia Xianzhu
马尔堡病毒(Marburg Virus，MARV)是世界上致死性出血热病毒之一，在人类和非人类灵长类动物中引起致命性出血热，死亡率高达90%。目前，还没有有效的治疗方法或批准的疫苗供人类使用来控制疾病的爆发和传播。病毒样颗粒(VLP)在形态上与天然的传染性病毒颗粒相同，可作为多种病毒的疫苗，包括人乳头瘤病毒(HPV)、猪圆环病毒(PCV)2型和乙肝病毒(HBV)。在本研究中，我们利用杆状病毒表达系统，通过共表达糖蛋白(GP)和基质蛋白(VP40)来产生Marv病毒样颗粒(VLP)。用马立克氏VLP与辅助剂茯苓多糖(PCP-II)混合接种恒河猴，可产生高达1：1280的GP特异性抗体效价和1：320的病毒中和抗体效价。通过酶联免疫斑点(ELISpot)检测，MARV VLP还可诱导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)和白介素4(IL-4)的分泌。这些数据表明，MARV VLP与PCP-II佐剂混合后在猕猴体内具有良好的免疫原性，有望成为一种有前景的MARV候选疫苗。
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-gamma(IFN-gamma) 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.