DNA vaccine initiates replication of live attenuated chikungunya virus in vitro and elicits protective immune response in mice.
DNA vaccine initiates replication of live attenuated chikungunya virus in vitro and elicits protective immune response in mice.
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DOI：
10.1093/infdis/jiu114
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发表时间：
2014-06
期刊：
影响因子：
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通讯作者：
I. Tretyakova;Jason Hearn;Eryu Wang;S. Weaver;P. Pushko
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文献类型：
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作者：
I. Tretyakova;Jason Hearn;Eryu Wang;S. Weaver;P. Pushko
基孔肯雅病毒（CHIKV）引起世界范围内的基孔肯雅热爆发，并代表了一种新的大流行威胁。针对CHIKV的疫苗开发已被证明具有挑战性。目前还没有批准的疫苗或针对该疾病的特定疗法。方法采用新型免疫DNA（iDNA）感染性克隆技术，结合DNA疫苗和减毒活疫苗的优点，研制新型实验性CHIKV疫苗。在此，我们描述了由质粒DNA组成的iDNA疫苗，所述质粒DNA编码真核启动子下游的活减毒CHIKV克隆181/25的全长感染性基因组。iDNA方法被设计为在体外和体内从质粒开始活疫苗病毒的复制。结果制备了实验性CHIKV iDNA疫苗，并在培养细胞和小鼠中进行了评价。用10 ng iDNA转染足以启动疫苗病毒的体外复制。用单个10 μg CHIKV iDNA质粒接种BALB/c小鼠导致血清转化、中和抗体的激发和免受神经毒性CHIKV的实验攻击的保护。结论CHIKV 181/25减毒活疫苗可通过DNA疫苗在体内外传递。iDNA方法似乎代表了CHIK和其他甲病毒疾病的有希望的疫苗接种策略。
BACKGROUND Chikungunya virus (CHIKV) causes outbreaks of chikungunya fever worldwide and represents an emerging pandemic threat. Vaccine development against CHIKV has proved challenging. Currently there is no approved vaccine or specific therapy for the disease. METHODS To develop novel experimental CHIKV vaccine, we used novel immunization DNA (iDNA) infectious clone technology, which combines the advantages of DNA and live attenuated vaccines. Here we describe an iDNA vaccine composed of plasmid DNA that encode the full-length infectious genome of live attenuated CHIKV clone 181/25 downstream from a eukaryotic promoter. The iDNA approach was designed to initiate replication of live vaccine virus from the plasmid in vitro and in vivo. RESULTS Experimental CHIKV iDNA vaccines were prepared and evaluated in cultured cells and in mice. Transfection with 10 ng of iDNA was sufficient to initiate replication of vaccine virus in vitro. Vaccination of BALB/c mice with a single 10 μg of CHIKV iDNA plasmid resulted in seroconversion, elicitation of neutralizing antibodies, and protection from experimental challenge with a neurovirulent CHIKV. CONCLUSIONS Live attenuated CHIKV 181/25 vaccine can be delivered in vitro and in vivo by using DNA vaccination. The iDNA approach appears to represent a promising vaccination strategy for CHIK and other alphaviral diseases.