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研发和临床评估多种研究用单价登革热疫苗,以确定用于四价减毒活疫苗的成分。

Development and clinical evaluation of multiple investigational monovalent DENV vaccines to identify components for inclusion in a live attenuated tetravalent DENV vaccine.

机构信息

Center for Immunization Research, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, United States.

出版信息

Vaccine. 2011 Sep 23;29(42):7242-50. doi: 10.1016/j.vaccine.2011.07.023. Epub 2011 Jul 21.

Abstract

The Laboratory of Infectious Diseases at the National Institute of Allergy and Infectious Diseases, National Institutes of Health has been engaged in an effort to develop a safe, efficacious, and affordable live attenuated tetravalent dengue vaccine (LATV) for more than ten years. Numerous recombinant monovalent DENV vaccine candidates have been evaluated in the SCID-HuH-7 mouse and in rhesus macaques to identify those candidates with a suitable attenuation phenotype. In addition, the ability of these candidates to infect and disseminate in Aedes mosquitoes had also been determined. Those candidates that were suitably attenuated in SCID-HuH-7 mice, rhesus macaques, and mosquitoes were selected for further evaluation in humans. This review will describe the generation of multiple candidate vaccines directed against each DENV serotype, the preclinical and clinical evaluation of these candidates, and the process of selecting suitable candidates for inclusion in a LATV dengue vaccine.

摘要

美国国立卫生研究院过敏和传染病研究所传染病实验室十多年来一直致力于开发一种安全、有效且负担得起的四价减毒活登革热疫苗(LATV)。已经在 SCID-HuH-7 小鼠和恒河猴中评估了许多重组单价 DENV 疫苗候选物,以确定具有合适减毒表型的候选物。此外,还确定了这些候选物在埃及伊蚊中感染和传播的能力。在 SCID-HuH-7 小鼠、恒河猴和蚊子中适当减毒的候选物被选择用于进一步在人类中进行评估。这篇综述将描述针对每种 DENV 血清型的多种候选疫苗的产生、这些候选物的临床前和临床评估,以及选择合适的候选物纳入 LATV 登革热疫苗的过程。

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