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：
10223114
负责人：
Matthew Adrian Coleman
金额：
$ 68.71万
依托单位：
UNIVERSITY OF CALIF-LAWRNC LVRMR NAT LAB
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/10223114
关键词：
Adjuvant Affect Antigen Presentation Antigens Apolipoproteins Bioinformatics Biological 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 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 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

Adjuvant Affect Antigen Presentation Antigens Apolipoproteins Bioinformatics Biological 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 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 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

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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：纳米脂蛋白支持的多亚基疫苗至沙眼衣原体项目摘要沙眼衣原体是最常见的细菌性传播感染（STI），影响超过130 每年有百万人，也是全球可预防失明的最常见原因。在曼联由C. c. c. c.造成的状态是数十亿美元的年成本（Gunn等，1998）。因为感染可能是无症状的，它可能没有治疗多年，并且可能导致后遗症，包括盆腔炎症性疾病，慢性腹痛，异位妊娠和不育。所以，公共卫生的紧迫性需要疫苗以预防由梭状芽孢杆菌引起的疾病。尽管开发衣原体疫苗的巨大努力，没有人出现。研究表明衣原体主要外膜蛋白（MOMP）免疫可诱导明显的保护如果保留了其天然结构，则针对小鼠和非人类灵长类动物的感染和疾病。但是，鉴于该蛋白具有16个跨膜，MOMP疫苗的配方是一个主要障碍域是40％疏水，作为同构二聚体组装，并包含多种半胱氨酸二硫键。我们现在已经证明，我们可以生产多聚物体，耐SDS，并且使用纳米脂蛋白颗粒（NLP）的MOMP的活性形式。此外，我们也第一次可以产生全长衣原体多态性膜蛋白（PMP），另一组衣原体表面表现出有效免疫原性的抗原。编码的蛋白质可以设计为血清特定于制造与沙眼衣原体相关的减轻影响的多旋转疫苗致病性。最后，我们开发了将MOMP与佐剂相结合的方法，以提供独特的在小鼠挑战研究中具有保护性的疫苗配方。这个最初的突破是通过将MOMP和PMP的合成生物学方法和无细胞共表达与载脂蛋白结合在一起。该提案的重点是进一步扩展MOMP与相关PMP的介绍，所有这些都在内 NLP，以实现针对衣原体感染的高度保护性疫苗。