Combination Vaccine Against Multiple STDs

针对多种性传播疾病的联合疫苗

• 批准号: 7153827
• 负责人: Francis O. Eko
• 金额: $ 13.7万
• 依托单位: MOREHOUSE SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7153827
• 关键词: Chlamydia trachomatis; Herpes simplex disease; Herpesviridae vaccine; Vibrio cholerae; bacterial antigens; bacterial vaccines; biological models; biotechnology; chlamydial disease; communicable disease control; drug delivery systems; herpes simplex virus 2; laboratory mouse; recombinant proteins; sexually transmitted diseases; vaccine development; vaccine evaluation; vector vaccine; virus antigen; virus protein

Sexually transmitted diseases (STDs) are of major medical and social importance worldwide, affecting about 500 million people annually, with debilitating or life-threatening consequences. Genital infections caused by Chlamydia trachomatis and Herpes simplex virus type 2 (HSV-2) rank among the highest STDs in the world. Genital chlamydial infection is the most common bacterial STD in the United States with severe irreversible complications in women, including pelvic inflammatory disease, fallopian tube scarring, ectopic pregnancy and infertility. Four million reported annual cases involve over $2 billion in treatment cost. Genital herpes is a widespread STD with severe complications, especially in neonates and immunocompromised individuals, including neonatal herpes and central nervous system involvement. Of the current control and prevention strategies, including early detection and treatment, vaccines capable of protecting against infection or severe disease would be the most effective long-term option to control diseases due to Chlamydia and HSV-2. A vaccine offers the best approach to protect the greatest number of people against infection. There is currently no licensed vaccine against either Chlamydia or herpes infections. Considering the high incidence of coinfections by both C. trachomatis and HSV-2, the availability of a combination vaccine that can be administered as a single regimen to protect against multiple infections would be highly desirable. Efficacious vaccines against Chlamydia and genital herpes would require identification of appropriate antigens and development of effective delivery vehicles capable of eliciting long-lasting protective immunity. We have designed a novel recombinant bacterial ghost delivery system which has inherent adjuvant properties and capable of simultaneously delivering multiple antigens from the same or different pathogens to the immune system. This proposal describes the use of the novel recombinant Vibrio cholerae ghost (rVCG) technology to develop a multivalent subunit combination vaccine comprising select outer membrane proteins (OMPs) including the highly immunogenic major OMP (MOMP) and PorB of C. trachomatis and the glycoprotein D (gD2) and B (gB2) of HSV-2. The hypothesis to be investigated is that immunization with a multivalent combination vaccine composed of rVCG expressing subunit antigens from both Chlamydia and HSV- 2 will simultaneously induce protective immunity against both genital Chlamydia and herpes infections. We have chosen MOMP, PorB, gD2 and gB2 as appropriate immunogens since these antigens contain protective T cell and neutralizing epitopes. Our aims are to: (a) genetically design an rVCG vectorbased multivalent subunit combination vaccine, and (b) assess the immunogenicity and protective efficacy of this vaccine construct in an appropriate animal model. Results from these studies will likely lead to the development of a reliable combination vaccine regimen against Chlamydia and HSV-2, which should have major implications for the control of STDs and their complications.

性传播疾病（STD）在全球范围内具有重要的医学和社会重要性，影响 每年有5亿人，带来衰弱或威胁生命的后果。由 衣原体沙眼和单纯疱疹病毒2型（HSV-2）列为世界上最高的性病之一。 生殖器衣原体感染是美国最常见的细菌性病 女性的并发症，包括骨盆炎性疾病，输卵管疤痕，异位妊娠 和不育。报告的年案件有400万例涉及超过20亿美元的治疗费用。生殖器疱疹是 广泛的性病患有严重并发症，尤其是在新生儿和免疫功能低下的个体中， 包括新生儿疱疹和中枢神经系统参与。当前的控制和预防 策略，包括早期检测和治疗，能够防止感染或严重的疫苗 由于衣原体和HSV-2，疾病将是控制疾病的最有效的长期选择。一个 疫苗提供了保护最大人数免受感染的最佳方法。目前有 没有针对衣原体或疱疹感染的许可疫苗。考虑共同感染的高发病率 通过沙眼梭状疱疹和HSV-2，可以使用的组合疫苗可以是 高度需要作为单一方案进行治疗以防止多种感染。有效 针对衣原体和生殖器疱疹的疫苗需要鉴定适当的抗原和 开发有效的递送车辆，能够引发长期的保护性免疫。我们有 设计了一种新型的重组细菌幽灵递送系统，该系统具有固有的佐剂特性和 能够同时将多种抗原从相同或不同的病原体传递到免疫 系统。该提案描述了新颖的重组颤音霍乱幽灵（RVCG）技术的使用 开发包括选择外膜蛋白（OPPS）的多价亚基组合疫苗 包括高度免疫原性的大型OMP（MOMP）和糖蛋白蛋白酶D HSV-2的（GD2）和B（GB2）。要研究的假设是具有多价的免疫 由RVCG组成的组合疫苗，这些疫苗表达来自衣原体和HSV-的亚基抗原 2同时诱发保护性免疫，以防止生殖器衣原体和疱疹 感染。我们选择了MOMP，PORB，GD2和GB2作为适当的免疫原子 包含保护性T细胞和中和表位。我们的目的是：（a）基于RVCG载体的基因设计 多价亚基组合疫苗，（b）评估免疫原性和保护性 这种疫苗在适当的动物模型中构建。这些研究的结果可能会导致 开发针对衣原体和HSV-2的可靠组合疫苗方案，该方案应具有 控制性病及其并发症的主要影响。