ChimeriVax-West Nile virus live-attenuated vaccine: Preclinical evaluation of safety, immunogenicity, and efficacy
ChimeriVax-West Nile virus live-attenuated vaccine: Preclinical evaluation of safety, immunogenicity, and efficacy
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DOI：
10.1128/jvi.78.22.12497-12507.2004
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发表时间：
2004-11-01
影响因子：
5.4
通讯作者：
Monath, TP
中科院分区：
文献类型：
--
作者：
Arroyo, J;Miller, C;Monath, TP
1999年在北美首次发现西尼罗病毒时，ChimeriVax疫苗技术可用于递送黄病毒保护性抗原，这有助于快速开发本文所述的西尼罗病毒候选疫苗。ChimeriVax-Japanese encephalitis （JE）是用该技术开发的首个减毒活疫苗，已成功通过I期和11项临床试验。ChimeriVax技术利用黄热病病毒（YF） 17D疫苗株的衣壳和非结构基因，将其他黄病毒的包膜基因作为减毒嵌合活病毒传递。乙脑病毒与西WN病毒包膜蛋白(E)氨基酸序列的同源性有助于针对减毒突变位点研制西WN病毒疫苗。在这里，我们讨论了ChimeriVax-WN病毒在小鼠和猕猴中的临床前研究。在小鼠和非人灵长类动物中，ChimeriVax-WN病毒疫苗的神经毒性低于商业化的YF 17D疫苗。病毒的衰减是由含有YF 17D病毒主干的衰减突变和引入改变WN病毒E蛋白基因残基107、316和440的三点突变的结构的嵌合性质决定的。ChimeriVax-WNO2疫苗在猕猴模型中的安全性、免疫原性和有效性表明，该候选疫苗有望对人类具有安全性和免疫原性。
The availability of ChimeriVax vaccine technology for delivery of flavivirus protective antigens at the time West Nile (WN) virus was first detected in North America in 1999 contributed to the rapid development of the vaccine candidate against WN virus described here. ChimeriVax-Japanese encephalitis (JE), the first live-attenuated vaccine developed with this technology has successfully undergone phase I and 11 clinical trials. The ChimeriVax technology utilizes yellow fever virus (YF) 17D vaccine strain capsid and nonstructural genes to deliver the envelope gene of other flaviviruses as live-attenuated chimeric viruses. Amino acid sequence homology between the envelope protein (E) of JE and WN viruses facilitated targeting attenuating mutation sites to develop the WN vaccine. Here we discuss preclinical studies with the ChimeriVax-WN virus in mice and macaques. ChimeriVax-WN virus vaccine is less neurovirulent than the commercial YF 17D vaccine in mice and nonhuman primates. Attenuation of the virus is determined by the chimeric nature of the construct containing attenuating mutations in the YF 17D virus backbone and three point mutations introduced to alter residues 107, 316, and 440 in the WN virus E protein gene. The safety, immunogenicity, and efficacy of the ChimeriVax-WNO2 vaccine in the macaque model indicate the vaccine candidate is expected to be safe and immunogenic for humans.