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（申请人提供）： 龋齿是由变形链球菌引起的传染病。尽管工业化国家进行了氟化处理并改善了牙齿卫生，但世界范围内的牙科群体仍然是一个重大的公共卫生问题，影响着 50-90% 的人口（0Nodd Health Organization）。在美国，59% 的一年级学生至少有一个蛀牙，三分之一的成年人每年不去​​看牙医，24% 的老年人经历与龋齿相关的牙齿脱落（美国口腔健康）。动物研究表明，这种疾病可以通过使用变形链球菌抗原进行免疫来预防。应用基因克隆技术生产重组菌、主动免疫用蛋白疫苗、肽疫苗和被动免疫用抗体。这些疫苗实现了不同程度的保护。考虑到面临风险的人群大多来自社会经济地位较低的群体（卫生局局长报告，美国 DHHS，2000 年），因此需要找到降低大规模免疫疫苗生产成本的方法。一种可能性是用含有目的基因的质粒 DNA (cDNA) 直接免疫，并在宿主中获得目标蛋白的表达。因此，避免了从重组克隆中分离昂贵的蛋白质。目前研究的长期目标是制备一种有效、安全且经济的 Dental Cades 疫苗。拟议期间的具体目标是探索针对变形链球菌的 DNA 疫苗的前景，特别强调与相应的蛋白质疫苗的功效、持续时间和成本进行比较。作为模型，将使用变形链球菌抗原 A (AgA)（一种公认的候选疫苗抗原）及其前体壁相关蛋白 A (WapA)（一种参与牙菌斑定植和形成的因子）。所提出的工作得到了生产 WapA 和 AgA 蛋白疫苗、wapA-pDNA 和 agA-pDNA 疫苗所需的重组克隆的可用性，以及用这些 pDNA 构建体转染的哺乳动物细胞中 WapA 和 AgA 的表达的支持。获得的结果将确定针对龋齿的基因免疫的可行性和成本效益，并且所进行的工作将作为针对通过粘膜表面侵入人体的其他传染源的疫苗研究的模型。