CHLAMYDIA DNA VACCINE: TESTING NEW PROTECTIVE ANTIGENS

我们建议使用衣原体基因组计划数据库中的信息克隆和表征新的衣原体基因，并测试其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6种抗原，这些抗原是根据在衣原体感染存活动物中证明的免疫原性选择的。这种免疫原性表明它们在用作亚单位疫苗时产生保护性免疫应答的潜力。我们现正寻求拨款，以进行这项计划的第二阶段。我们现在计划测试这六个抗原序列，单独和组合，它们在小鼠中产生体液和细胞免疫的潜力。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DNA肌内和鼻内给药进行检测和比较。然后通过衣原体攻击检测发现具有免疫原性的抗原的保护性免疫力。已在内部确定了动物的沙眼衣原体感染，并将对接种动物的鼻内和阴道内攻毒进行检测。拟议的商业应用：目前还没有预防衣原体感染的有效疫苗。据估计，美国每年有300万新感染者，导致超过30亿美元的相关医疗费用。这些数字不包括世界范围内的沙眼感染。在美国之外，衣原体感染是可预防失明的主要原因。这项应用中的拟议研究是开发有效的衣原体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.