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首页> 外文期刊>PLOS Neglected Tropical Diseases >A DNA Vaccine against Chikungunya Virus Is Protective in Mice and Induces Neutralizing Antibodies in Mice and Nonhuman Primates
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A DNA Vaccine against Chikungunya Virus Is Protective in Mice and Induces Neutralizing Antibodies in Mice and Nonhuman Primates

机译:针对基孔肯雅病毒的DNA疫苗对小鼠具有保护作用,并在小鼠和非人类灵长类动物中诱导中和抗体。

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Chikungunya virus (CHIKV) is an emerging mosquito-borne alphavirus indigenous to tropical Africa and Asia. Acute illness is characterized by fever, arthralgias, conjunctivitis, rash, and sometimes arthritis. Relatively little is known about the antigenic targets for immunity, and no licensed vaccines or therapeutics are currently available for the pathogen. While the Aedes aegypti mosquito is its primary vector, recent evidence suggests that other carriers can transmit CHIKV thus raising concerns about its spread outside of natural endemic areas to new countries including the U.S. and Europe. Considering the potential for pandemic spread, understanding the development of immunity is paramount to the development of effective counter measures against CHIKV. In this study, we isolated a new CHIKV virus from an acutely infected human patient and developed a defined viral challenge stock in mice that allowed us to study viral pathogenesis and develop a viral neutralization assay. We then constructed a synthetic DNA vaccine delivered by in vivo electroporation (EP) that expresses a component of the CHIKV envelope glycoprotein and used this model to evaluate its efficacy. Vaccination induced robust antigen-specific cellular and humoral immune responses, which individually were capable of providing protection against CHIKV challenge in mice. Furthermore, vaccine studies in rhesus macaques demonstrated induction of nAb responses, which mimicked those induced in convalescent human patient sera. These data suggest a protective role for nAb against CHIKV disease and support further study of envelope-based CHIKV DNA vaccines.
机译:基孔肯雅病毒(CHIKV)是热带非洲和亚洲的一种由蚊子传播的新兴甲型病毒。急性疾病的特征是发烧,关节痛,结膜炎,皮疹,有时甚至是关节炎。对于免疫的抗原靶标知之甚少,并且目前尚无用于该病原体的许可疫苗或治疗剂。虽然埃及伊蚊是其主要媒介,但最近的证据表明,其他携带者也可以传播CHIKV,从而引起人们对其在自然流行地区之外向包括美国和欧洲在内的新国家传播的担忧。考虑到大流行的可能性,了解免疫力的发展对于制定针对CHIKV的有效对策至关重要。在这项研究中,我们从一名急性感染的人类患者中分离出了新的CHIKV病毒,并在小鼠中开发了明确的病毒攻击原种,从而使我们能够研究病毒的发病机理并开展病毒中和试验。然后,我们构建了一种通过体内电穿孔(EP)递送的合成DNA疫苗,该疫苗表达了CHIKV包膜糖蛋白的一种成分,并使用该模型评估其功效。疫苗接种诱导了强大的抗原特异性细胞和体液免疫反应,这些反应分别能够为小鼠抵抗CHIKV攻击提供保护。此外,在恒河猴中进行的疫苗研究表明,诱导了nAb反应,该反应模仿了在恢复期人类患者血清中诱导的反应。这些数据表明nAb对CHIKV疾病具有保护作用,并支持对基于包膜的CHIKV DNA疫苗的进一步研究。

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