Recombinant Multivalent Subunit Combination Vaccine Against Multiple STDs

针对多种 STD 的重组多价亚基组合疫苗

• 批准号: 7491791
• 负责人: Francis O. Eko
• 金额: $ 6.63万
• 依托单位: MOREHOUSE SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7491791
• 关键词: Adjuvant; Adjuvanticity; Affect; Animal Model; Annual Reports; Antibodies; Antigen Targeting; Antigens; Bacteria; Bacterial Sexually Transmitted Diseases; Chlamydia; Chlamydia Infections; Chlamydia trachomatis; Cicatrix; Cloning; Combined Vaccines; Development; Disease; Early Diagnosis; Ectopic Pregnancy; Epitopes; Erythrocyte Ghost; Etiology; Evaluation; Frequencies; Genes; Genital system; Glycoproteins; Goals; Health Care Costs; Human Herpesvirus 2; Immune response; Immune system; Immunity; Immunization; Immunocompetent; Immunocompromised Host; Incidence; Individual; Infection; Infertility; Intramuscular; Laboratories; Lead; Licensing; Life; Mammalian Oviducts; Medical; Membrane Proteins; Morbidity - disease rate; Mucous Membrane; Mus; Neonatal; Neuraxis; Numbers; Pelvic Inflammatory Disease; Prevention strategy; Production; Property; Protein C; Proteins; Recombinants; Reproductive Health; Route; Secretory Cell; Sexually Transmitted Diseases; Simplexvirus; System; T-Lymphocyte; Technology; Testing; Treatment Cost; Treatment Protocols; United States; Vaccinated; Vaccine Design; Vaccines; Vibrio cholerae; Vibrio cholerae O1; Viral; Woman; base; design; disorder control; genital herpes; genital infection; immunogenic; immunogenicity; major outer membrane protein; mouse model; neonate; novel; pathogen; response; social; vaccine efficacy

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）在世界范围内具有重大的医学和社会意义，约有 每年有5亿人死亡，造成衰弱或危及生命的后果。生殖器感染的原因 沙眼衣原体和单纯疱疹病毒2型（HSV-2）是世界上最常见的性病。 生殖器衣原体感染是美国最常见的细菌性性病， 女性并发症，包括盆腔炎、输卵管瘢痕、异位妊娠 和不孕不育。每年报告的400万例病例涉及超过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，伴有严重并发症，尤其是新生儿和免疫功能低下的个体， 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， 疾病将是控制由衣原体和HSV-2引起的疾病的最有效的长期选择。一 疫苗是保护最多人免受感染的最佳途径。目前 没有针对衣原体或疱疹感染的许可疫苗。考虑到合并感染的高发生率 两个C。沙眼和HSV-2，一种组合疫苗的可用性， 作为单一方案施用以防止多种感染将是非常期望的。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， 开发能够引发持久保护性免疫的有效运载工具。我们有 设计了一种新的重组细菌血影递送系统，其具有固有的佐剂性质， 能够同时将来自相同或不同病原体的多种抗原递送至免疫系统 系统该提案描述了新的重组霍乱弧菌鬼（rVCG）技术的使用 开发包含选择的外膜蛋白（OMP）的多价亚单位组合疫苗， 包括C.沙眼衣原体和糖蛋白D (gD2)和HSV-2的B（gB 2）。待研究的假设是，用多价抗体免疫 由表达来自衣原体和HSV的亚单位抗原的rVCG组成的联合疫苗- 2将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MOMP、PorB、gD 2和gB 2作为合适的免疫原，因为这些抗原 含有保护性T细胞和中和表位。我们的目标是：（a）基因设计一个rVCG载体， 多价亚单位组合疫苗，和（B）评估免疫原性和保护效力 在适当的动物模型中构建该疫苗。这些研究的结果可能会导致 开发一种可靠的针对衣原体和单纯疱疹病毒-2的联合疫苗方案，该方案应该 对控制性病及其并发症的重大影响。