Efficacy of DNA versus Protein Vaccine

DNA 疫苗与蛋白质疫苗的功效对比

• 批准号: 6570904
• 负责人: MYLIEN DAO
• 金额: $ 14.5万
• 依托单位: UNIVERSITY OF SOUTH FLORIDA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-15 至 2005-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6570904
• 关键词: Streptococcus mutans; bacterial antigens; cost effectiveness; dental caries vaccine; dosage; immunoglobulin A; immunomodulators; laboratory mouse; laboratory rabbit; molecular cloning; mucosal immunity; vaccine development; vector vaccine

DESCRIPTION (provided by applicant): Dental caries is an infectious disease caused by Streptococcus mutans. Despite fluoridation and improved Dental hygiene in industrialized countries, worldwide Dental cades is still a significant public health problem affecting 50-90 percent of the population 0Nodd Health Organization). In the United Sates of America, 59 percent of first graders have at least one cavity, one third of the adult population does not see a Dentist annually, and 24 percent of the elderly experience caries-associated tooth loss (Oral Health America). Animal studies demonstrated that this disease was preventable by immunization with so mutans antigens. Gene cloning technology was applied to produce recombinant bacteria, protein and peptide vaccines for active immunization, and antibody for passive immunization. Various levels of protection were achieved with these vaccines. Considering that the population at risk is mostly from low socioeconomic groups (Surgeon General's report, U.S. DHHS, 2000), it is desirable to find means to lower the costs of vaccine production for mass immunization. One possibility is to directly immunize with a plasmid DNA (cDNA) containing the gene(s) of interest and obtain expression of the target protein(s) in the host. Thus, expensive protein isolation from recombinant clones is avoided. The Long Term Goal of the current study is to prepare an efficacious, safe and economical Dental Cades vaccine. The Specific Aim for the proposed period is to explore the prospect of a DNA vaccine against S. mutans with special emphasis on comparing the efficacy, duration and costs with those of corresponding Protein Vaccine. As models, the S. mutans antigen A (AgA), a recognized candidate vaccine antigen, and its precursor the wall-associated protein A (WapA), a factor involved in colonization and buildup of Dental plaque, will be used. The work proposed is supported by the availability of the recombinant clones needed for the production of WapA and AgA protein vaccines, and wapA-pDNA and agA-pDNAvaccines, and by the expression of WapA and AgA in mammalian cells transfected with these pDNA constructs. The results obtained will determine the feasibility and cost-effectiveness of genetic immunization against Dental caries, and the work performed will serve as a model for vaccine research against other infectious agents invading the body through mucosal surfaces.

描述（由申请人提供）：龋齿是由链球菌突变引起的一种传染病。尽管工业化国家的氟化和牙齿卫生改善，但全球牙科菜仍然是影响50-90％人口0NODD卫生组织的重大公共卫生问题）。在美国的联合面积中，有59％的一年级学生至少有一个空腔，三分之一的成年人人口没有看到牙医，而24％的老年人经历了与龋齿相关的牙齿脱落（美国口腔健康）。动物研究表明，这种疾病是可以通过SO抗原免疫来预防的。基因克隆技术用于生产重组细菌，蛋白质和肽疫苗进行主动免疫，以及用于被动免疫的抗体。这些疫苗实现了各种保护水平。考虑到有危险的人口主要来自低社会经济群体（外科医生的报告，美国DHHS，2000年），希望找到降低疫苗生产成本以进行大规模免疫的方法。一种可能性是用含有感兴趣的基因的质粒DNA（cDNA）直接免疫，并在宿主中获得靶蛋白的表达。因此，避免了从重组克隆中分离出昂贵的蛋白质。当前研究的长期目标是准备有效，安全和经济的牙科疫苗。拟议时期的具体目的是探索针对链球菌的DNA疫苗的前景，特别强调将功效，持续时间和成本与相应蛋白疫苗的疗效，持续时间和成本进行比较。作为模型，将使用抗原抗原A抗原A（AGA），公认的候选疫苗抗原及其前体壁相关蛋白A（WAPA），这是与牙菌斑的定殖和堆积有关的因素。提出的工作得到了生产WAPA和AGA蛋白疫苗所需的重组克隆，WAPA-PDNA和AGA-PDNAVACCINE所需的重组克隆的支持，以及用这些PDNA构建体转染的哺乳动物细胞中WAPA和AGA在哺乳动物细胞中的表达。获得的结果将确定针对龋齿的遗传免疫的可行性和成本效益，并且所进行的工作将作为针对其他通过粘膜表面侵入人体的传染剂研究的疫苗研究模型。