以生物信息学手段设计登革亚单位疫苗的研究

Dengue fever is a re-emerging viral disease caused by dengue viruses that are transmitted by mosquitoes. It causes millions of cases of dengue fever,dengue hemorrhagic fever and dengue shock syndrome woldwide. Although efforts have been made to develop dengue vaccines, no licensed one is available. The major challenge confronting dengue vaccine development is to induce a balanced and long lasting immunity against four co-circulating virus serotype(DENV-I, II, III, IV), infection by any of which may lead to more severe disease in a heterotypic secondary infection. In this proposal, we aim to develop a tetravalent subunit vaccine with consensus 80% Envelope(E) protein sequence which is calculated from thousands of sequences of all four serotype of dengue viruses. Using the baculovirus expression system, 80% Envelope proteins of four serotype virus and consensus 80%E protein will be prepared. The immunogenicity and protective efficacy of the single consensus 80%E (E80) and the standard tetravalent E80s, will be evaluated and compared in Balb/c mice and AG129 mice.This project will set foundation for further macaque or clinical studies, and make major contributions to the development of next-generation dengue vaccine.

登革病毒是一种通过蚊虫传播的病原体，它可引起登革热、登革出血热及登革热休克综合症等急性传染病,四种血清型病毒在全球流行并引发疫情。作为一种新发传染性致病原，登革病毒已逐渐受到广泛重视。尽管经历了多年研究，目前仍无有效的登革疫苗投入应用。针对登革四种血清型病毒并存流行，二次异型感染增强病症，及登革疫苗需诱导均衡持久免疫反应等特点，本项目计划研发覆盖四种血清型的登革病毒膜泡(E)蛋白共有序列重组疫苗，并评价其相较于传统四价疫苗的优势。四种血清型E蛋白的可溶区域80%E和共有序列80%E将在杆状病毒系统中制备，用以检测比较单价80%E，四价80%E，及共有序列80%E分别免疫Balb/c小鼠时的免疫原性。同时通过被动免疫和攻毒,比较三类抗原在AG129小鼠中的体内保护性。此项目将为后续登革亚单位疫苗在大动物乃至临床实验中的免疫和保护效果奠定基础，为新型登革疫苗的研究做出贡献。