Immunogenicity of a Japanese encephalitis DNA vaccine candidate in cynomolgus monkeys.
Immunogenicity of a Japanese encephalitis DNA vaccine candidate in cynomolgus monkeys.
复制标题
日本脑炎 DNA 候选疫苗在食蟹猴中的免疫原性。
DOI：
10.1016/s0264-410x(03)00079-3
复制
发表时间：
2003
期刊：
影响因子：
5.5
通讯作者：
Konishi,Eiji
中科院分区：
文献类型：
--
作者：
Tanabayashi,Kiyoshi;Mukai,Ryozaburo;Yamada,Akio;Takasaki,Tomohiko;Kurane,Ichiro;Yamaoka,Masaoki;Terazawa,Aya;Konishi,Eiji
对编码乙脑病毒前膜(PrM)和包膜(E)基因的乙脑疫苗候选疫苗pNJEME在非人类灵长类动物食蟹猴中的安全性和免疫原性进行了评价。PNJEME是用载体(PNGVL4a)构建的，旨在解决DNA疫苗的一些安全问题。在两个不同的实验中，两种不同的免疫方法是肌肉注射300μg的pNJEME。3μg基因枪注射，3次肌肉注射免疫。注射pNJEME500μg。三种方案均可诱导低水平至高水平的中和抗体，表明pNJEME具有诱导猴产生中和抗体的能力，但对pNJEME的反应个体差异较大。在一项旨在将DNA疫苗与商业化灭活乙脑疫苗进行比较的实验中，有三种疫苗是通过肌肉注射进行免疫的。用300μg的pNJEME接种或用3μg的pNJEME基因枪接种，在大多数猴子中产生的中和抗体水平与人剂量灭活疫苗三次免疫所诱导的中和抗体水平相似。用北京P3株或JaTH160株乙脑病毒鼻内攻击后，pNJEME免疫的猕猴表现出记忆中和抗体反应，表明pNJEME诱导了对乙脑病毒感染有反应的记忆B细胞。免疫后未观察到任何猴子的全身和局部反应。或者用基因枪接种质粒DNA。
A Japanese encephalitis (JE) vaccine candidate encoding JE virus premembrane (prM) and envelope (E) genes, designated pNJEME, was evaluated for safety and immunogenicity in non-human primate, cynomolgus monkeys. pNJEME was constructed using a vector (pNGVL4a) designed to address some of the safety concerns of DNA vaccine. In two different experiments, two immunizations with 300μg of pNJEME by intramuscular (i.m.) injection, and 3μg of pNJEME using a gene gun, and three immunizations by i.m. injection with 500μg of pNJEME were performed. All the three protocols induced low to high levels of neutralizing antibody, indicating an ability of pNJEME to induce neutralizing antibody in monkeys with a wide individual variation in response to pNJEME. In one experiment designed to compare the DNA vaccine with a commercial inactivated JE vaccine, three immunizations by i.m. inoculation with 300μg of pNJEME or by gene gun administration with 3μg of pNJEME induced similar levels of neutralizing antibody to those induced by three immunizations with a human dose of the inactivated vaccine in most monkeys. After intranasal challenge with the Beijing P3 or JaTH160 strain of JE virus, pNJEME-immunized monkeys showed anamnestic neutralizing antibody responses, indicating that pNJEME induced memory B cells which were responsive to infection with JE virus. No systemic and local reactions were observed in any monkeys after i.m. or gene gun inoculations with plasmid DNAs.