Immunization with plasmid DNA encoding the envelope glycoprotein of Japanese Encephalitis virus confers significant protection against intracerebral viral challenge without inducing detectable antiviral antibodies
Immunization with plasmid DNA encoding the envelope glycoprotein of Japanese Encephalitis virus confers significant protection against intracerebral viral challenge without inducing detectable antiviral antibodies
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DOI：
10.1016/s0264-410x(99)00180-2
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发表时间：
1999-08-20
期刊：
影响因子：
5.5
通讯作者：
Rangarajan, PN
中科院分区：
文献类型：
--
作者：
Ashok, MS;Rangarajan, PN
质粒DNA构建体。构建了编码日本脑炎病毒（JEV）包膜糖蛋白的pCMXENV。当转染到培养的Vero细胞中时，该质粒在细胞内表达E蛋白。使用脑内（i.c.）JEV挑战模型。进行了几次独立的免疫和JEV攻击实验，结果表明51%和59%的小鼠被保护免于致死的i. c. JEV攻击，当用pCMXENV通过肌内（i.m.）和鼻内（i.n.）路分别。用载体DNA（pCMX）免疫的小鼠在这些实验中均未存活。在pCMXENV免疫的小鼠中在攻击之前或之后均未检测到JEV特异性抗体。在用pCMXENV免疫的小鼠中观察到JEV特异性T细胞，其在JEV攻击后显著增加，表明存在疫苗接种诱导的记忆T细胞。增强生产的干扰素-γ（IFN-γ）和完全没有白细胞介素-4（IL-4）在pCMXENV免疫小鼠的脾细胞再刺激与JEV抗原在体外表明，保护可能是介导的辅助性T细胞（Th）淋巴细胞的Th 1亚型。总之，我们的结果表明，用表达细胞内形式的JEV E蛋白的质粒DNA免疫可提供针对i.c.即使在没有可检测到的抗病毒抗体的情况下，也可以进行JEV攻毒。(C)1999由Elsevier Science Ltd.出版。保留所有权利。
A plasmid DNA construct. pCMXENV encoding the envelope (E) glycoprotein of Japanese Encephalitis virus (JEV), was constructed. This plasmid expresses the E protein intracellularly, when transfected into Vero cells in culture. The ability of pCMXENV to protect mice from lethal JEV infection was evaluated using an intracerebral (i.c.) JEV challenge model. Several independent immunization and JEV challenge experiments were carried out and the results indicate that 51 and 59% of the mice are protected from lethal i.c. JEV challenge, when immunized with pCMXENV via intramuscular (i.m.) and intranasal (i.n.) routes respectively. None of the mice immunized with the vector DNA (pCMX) survived in any of these experiments. JEV-specific antibodies were not detected in pCMXENV-immunized mice either before or after challenge. JEV-specific T cells were observed in mice immunized with pCMXENV which increased significantly after JEV challenge indicating the presence of vaccination-induced memory T cells. Enhanced production of interferon-gamma (IFN-gamma) and complete absence of interleukin-4 (IL-4) in splenocytes of pCMXENV-immunized mice on restimulation with JEV antigens in vitro indicated that the protection is likely to be mediated by T helper (Th) lymphocytes of the Th1 sub-type. In conclusion, our results demonstrate that immunization with a plasmid DNA expressing an intracellular form of JEV E protein confers significant protection against i.c. JEV challenge even in the absence of detectable antiviral antibodies. (C) 1999 Published by Elsevier Science Ltd. All rights reserved.