Pang X, Zhang M, Dayton A I
Laboratory of Molecular Virology, Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, FDA, Bethesda, MD, USA.
BMC Microbiol. 2001;1:18. doi: 10.1186/1471-2180-1-18. Epub 2001 Aug 24.
As part of a program to develop a Dengue virus vaccine which avoids the deleterious effects of antibody dependent enhancement (ADE) of infection mediated by antibodies to Dengue virus structural proteins, we have begun to investigate the possibility of designing Dengue vaccines based on non-structural proteins.
Dengue constructs which lack major structural proteins replicate intracellularly in tissue culture. These replicons are capable of prolonged expression of Dengue virus non-structural proteins for at least seven days in culture.
Dengue virus genomes lacking major structural proteins can, like other flaviviruses, replicate intracellularly and express virus non-structural proteins with minimal toxicity to host cells. These findings pave the way for the development of dengue virus replicons as a form of live, attenuated virus vaccine.
作为开发一种登革病毒疫苗计划的一部分,该疫苗旨在避免由针对登革病毒结构蛋白的抗体介导的感染的抗体依赖性增强(ADE)的有害影响,我们已开始研究基于非结构蛋白设计登革疫苗的可能性。
缺乏主要结构蛋白的登革构建体在组织培养中于细胞内复制。这些复制子能够在培养中持续表达登革病毒非结构蛋白至少七天。
缺乏主要结构蛋白的登革病毒基因组可以像其他黄病毒一样,在细胞内复制并表达病毒非结构蛋白,对宿主细胞的毒性最小。这些发现为开发登革病毒复制子作为一种减毒活病毒疫苗形式铺平了道路。