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Project 1. Nanolipoprotein-supported multi-subunit vaccine for Chlamydia trachomatis

项目1.纳米脂蛋白支持的沙眼衣原体多亚单位疫苗

基本信息

批准号：
10458654
负责人：
Matthew Adrian Coleman
金额：
$ 53.06万
依托单位：
LAWRENCE LIVERMORE NATIONAL SECURITY, LLC
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-08 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10458654
关键词：
Adjuvant Affect Antigen Presentation Antigens Apolipoproteins Bioinformatics Biomedical Engineering Blindness Cells Chlamydia Chlamydia Infections Chlamydia trachomatis Codon Nucleotides Collaborations Complex Coupled Cryoelectron Microscopy Cysteine Disease Disulfides Ectopic Pregnancy Engineering Formulation Genital Genitalia Hydrophobicity Immunization Immunology In Vitro Individual Infection Infertility Length Membrane Proteins Methods Mus Pathogenesis Pathogenicity Pathology Pelvic Inflammatory Disease Persons Plasmids Production Property Protein Engineering Proteins Protocols documentation Public Health Recombinants Research Research Project Grants Resistance Safety Sexually Transmitted Diseases Solubility Structure Subunit Vaccines Surface Antigens Technology Testing Time Translations Transmembrane Domain United States Vaccines Variant Western Blotting base chronic abdominal pain combinatorial cost immunogenicity long-term sequelae major outer membrane protein mimetics nano nanolipoprotein particles nanomembrane nanoparticle nonhuman primate novel pathogen preservation prevent protein complex protein expression protein folding protein purification protein structure safety testing scaffold scale up statistics synthetic biology vaccine candidate vaccine development vaccine formulation

项目摘要

Project Title: Nanolipoprotein supported multi-subunit vaccine to Chlamydia trachomatis Project Abstract Chlamydia trachomatis is the most common bacterial sexually transmitted infection (STI), affecting over 130 million people every year, and is the most common cause of preventable blindness worldwide. In the United States, STIs caused by C. trachomatis account for billions of dollars in annual costs (Gunn et al. 1998). Because the infection can be asymptomatic, it may go untreated for years and can result in long-term sequelae, including pelvic inflammatory disease, chronic abdominal pain, ectopic pregnancy, and infertility. Therefore, the pressing public health need for a vaccine to prevent diseases caused by C. trachomatis is clear. Despite considerable efforts to develop a chlamydial vaccine, none have been forthcoming. Studies have shown that immunization with the Chlamydia major outer membrane protein (MOMP) can induce significant protection against infection and disease in both mice and non-human primates if its native structure is preserved. However, formulation of MOMP vaccines is a major hurdle given that this protein has 16 transmembrane domains, is 40% hydrophobic, assembles as a homotrimer, and contains multiple cysteines that can form disulfide bridges. We have now demonstrated that we can produce a multi-oligomeric, SDS-resistant, and active form of MOMP using nanolipoprotein particles (NLPs). Furthermore, for the first time we can also produce full-length Chlamydia polymorphic membrane proteins (Pmps), another group of chlamydia surface antigens that have shown potent immunogenicity. The encoded proteins can be engineered to be serovar specific to make multi-serovar vaccines for mitigating affects associated with Chlamydia trachomatis pathogenicity. Finally, we have developed methods to combine MOMP with adjuvants to provide a unique vaccine formulation that was protective in mouse challenge studies. This initial breakthrough was achieved by combining synthetic biology approaches and cell-free co-expression of MOMP and PMPs with apolipoproteins. This proposal is focused on further extending MOMP presentation with associated PMPs, all formulated within NLPs, to achieve a highly protective vaccine against Chlamydia infections.

项目名称：纳米脂蛋白支持的沙眼衣原体多亚单位疫苗