DNA vaccine coding for the full-length infectious Kunjin virus RNA protects mice against the New York strain of West Nile virus
DNA vaccine coding for the full-length infectious Kunjin virus RNA protects mice against the New York strain of West Nile virus
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DOI：
10.1073/pnas.1834270100
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发表时间：
2003-09-02
影响因子：
11.1
通讯作者：
Khomykh, AA
中科院分区：
文献类型：
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作者：
Hall, RA;Nisbet, DJ;Khomykh, AA
使用质粒 DNA 指导昆金 (KUN) 病毒感染性全长 RNA 基因组从哺乳动物表达启动子在体内转录，对小鼠进行肌肉注射。质粒中编码的 KUN 病毒 cDNA 包含 NS1 蛋白的突变（Pro-250 至 Leu），先前显示该突变可在断奶小鼠中减弱 KUN 病毒。 DNA接种后3-4天，从免疫小鼠的血液中分离出KUN病毒，证明感染性RNA正在体内转录；然而，没有观察到病毒引起的疾病的症状。免疫后19天，在免疫动物的血清中检测到中和抗体。在脑内或腹膜内接受致死剂量的西尼罗河纽约毒株 (WN) 或野生型 KUN 病毒的攻击后，仅用 0.1-1 杯 KUN 质粒 DNA 免疫的小鼠就得到了强有力的保护，免受疾病侵害。这一发现与体外中和数据相关，表明来自 KUN DNA 免疫小鼠的血清以相似的效率中和 KUN 和 WN 病毒。结果表明，通过质粒 DNA 载体传递减毒但可复制的 KUN 病毒可能提供针对 WN 病毒毒株的有效疫苗接种策略。
A plasmid DNA directing transcription of the infectious full-length RNA genome of Kunjin (KUN) virus in vivo from a mammalian expression promoter was used to vaccinate mice intramuscularly. The KUN viral cDNA encoded in the plasmid contained the mutation in the NS1 protein (Pro-250 to Leu) previously shown to attenuate KUN virus in weanling mice. KUN virus was isolated from the blood of immunized mice 3-4 days after DNA inoculation, demonstrating that infectious RNA was being transcribed in vivo; however, no symptoms of virus-induced disease were observed. By 19 days postimmunization, neutralizing antibody was detected in the serum of immunized animals. On challenge with lethal doses of the virulent New York strain of West Nile (WN) or wild-type KUN virus intracerebrally or intraperitoneally, mice immunized with as little as 0.1-1 mug of KUN plasmid DNA were solidly protected against disease. This finding correlated with neutralization data in vitro showing that serum from KUN DNA-immunized mice neutralized KUN and WN,viruses with similar efficiencies. The results demonstrate that delivery of an attenuated but replicating KUN virus via a plasmid DNA vector may provide an effective vaccination strategy against virulent strains of WN virus.