CHLAMYDIA DNA VACCINE: TESTING NEW PROTECTIVE ANTIGENS

我们建议利用衣原体基因组计划数据库的信息克隆和表征新的衣原体基因，并测试它们作为亚单位疫苗的潜力。拟议项目的第一部分已经完成，并已鉴定出六种抗原，这些抗原是根据它们在衣原体感染存活的动物中表现出的免疫原性而选择的。这种免疫原性表明，当用作亚单位疫苗时，它们可能产生保护性免疫反应。我们现在寻求资金以进行该项目的第二阶段。我们现在计划测试这六种抗原序列，单独或组合，以测试它们在小鼠体内产生体液免疫和细胞免疫的潜力。编码这些抗原的“裸”质粒dna将用于给动物接种疫苗。将根据产生体液和/或细胞免疫的能力对肌肉和鼻内给药DNA进行测试和比较。被发现具有免疫原性的抗原将通过衣原体攻击进行保护性免疫测试。动物沙眼衣原体感染已在室内确定，将对接种疫苗的动物进行鼻内和阴道内感染试验。建议的商业应用：目前尚无预防衣原体感染的有效疫苗。据估计，美国每年有300万新感染病例，导致相关医疗费用超过30亿美元。这些数字不包括世界范围内的沙眼感染。在美国以外，衣原体感染是导致可预防失明的主要原因。在这项应用中提出的研究是开发针对衣原体的有效DNA疫苗的第一步。这种疫苗将在国际范围内立即产生广泛的商业需求。

We have proposed to use the information from the Chlamydia Genome Project database to clone and characterize new chlamydial genes and to test their potential as a subunit vaccine. The first part of the proposed project has been completed and has resulted in the identification of six antigens that were selected based on their demonstrated immunogenicity in animals surviving chlamydial infection. This immunogenicity indicates their potential for generating a protective immune response when used as a subunit vaccine. We now seek funding to proceed to the second stage of this project. We now plan to test these six antigen sequences, alone and in combination, for their potential to generate both humoral and cell based immunity in mice. "Naked" plasmid DNAs, encoding these antigens, will be used to vaccinate animals. Intramuscular and intranasal administration of DNA will be tested and compared based on the ability to generate humoral and/or cell-based immunity. Antigens found to be immunogenic will then be tested for protective immunity by a chlamydial challenge. Chlamydia trachomatis infection of animals have been established in- house and both intranasal and intravaginal challenges of vaccinated animals will be tested. PROPOSED COMMERCIAL APPLICATIONS: No effective vaccine for the prevention of chlamydial infections currently exists. There are an estimated 3 million new infections annually in the U.S., resulting in over $3 billion in associated health care costs. These figures do not include world-wide trachoma infections. Outside the U.S., chlamydial infections are the leading cause of preventable blindness. The proposed research in this application is the first step in the development of an effective DNA vaccine against chlamydia. Such a vaccine would have immediate, widespread commercial demand, on an international scale.