Recombinant Multivalent Subunit Combination Vaccine Against Multiple STDs

性传播疾病(STDS)在世界范围内具有重大的医学和社会意义，影响着大约 每年有5亿人，造成虚弱或危及生命的后果。由以下原因引起的生殖器感染 沙眼衣原体和单纯疱疹病毒2型(HSV-2)是世界上性病发病率最高的两种疾病之一。 生殖器衣原体感染是美国最常见的细菌性STD，具有严重的不可逆转 妇女的并发症，包括盆腔炎、输卵管疤痕、异位妊娠 和不孕不育。每年报告的400万个病例涉及超过20亿美元的治疗费用。生殖器疱疹是一种 广泛传播的性传播疾病，有严重的并发症，特别是在新生儿和免疫功能低下的人中， 包括新生儿疱疹和中枢神经系统受累。当前的控制和预防 战略，包括早期发现和治疗、能够预防感染或严重感染的疫苗 疾病将是控制由于衣原体和HSV-2引起的疾病的最有效的长期选择。一个 疫苗是保护最多的人免受感染的最好方法。目前有 没有获得许可的针对衣原体或疱疹感染的疫苗。考虑到混合感染的高发病率 沙眼衣原体和HSV-2的联合疫苗的可用性可以是 作为一种单一的方案来预防多种感染将是非常可取的。有效的 针对衣原体和生殖器疱疹的疫苗将需要识别适当的抗原和 开发能够激发持久保护性免疫的有效递送工具。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 能够同时将来自相同或不同病原体的多种抗原输送到免疫系统 系统。本提案描述了新的重组霍乱弧菌幽灵(RVCG)技术的应用 研制精选外膜蛋白(OMP)多价亚单位组合疫苗 包括沙眼衣原体高度免疫原性的主要膜蛋白(MOMP)和PorB以及糖蛋白D (GD2)和B(GB2)。要研究的假设是，用多价疫苗免疫 表达衣原体和单纯疱疹病毒亚单位抗原的rVCG联合疫苗 2会同时诱导对生殖器衣原体和疱疹的保护性免疫。 感染。我们选择了MOMP、PorB、GD2和GB2作为合适的免疫原 含有保护性T细胞和中和表位。我们的目标是：(A)从基因上设计基于rVCG的载体 多价亚单位联合疫苗，以及(B)评估疫苗的免疫原性和保护效果 该疫苗构建在一个合适的动物模型中。这些研究的结果可能会导致 开发一种可靠的衣原体和HSV-2联合疫苗方案，该方案应具有 对控制性传播疾病及其并发症的主要影响。

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.