Development of VesiVax Carbohydrate Conjugation Chemistry

VesiVax 碳水化合物共轭化学的发展

基本信息

批准号：
8593016
负责人：
Gary Fujii
金额：
$ 29.43万
依托单位：
MOLECULAR EXPRESS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-08-01 至 2015-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8593016
关键词：
Adjuvant Agonist Amines Animals Antibodies Antigen Targeting Antigens Bacteria Biological Body Weight decreased Buffers C-terminal Caliber Carbohydrates Chemistry Chimeric Proteins Chromatography Citrobacter freundii Communicable Diseases Conjugate Vaccines Coupled Couples Coupling Cyclic GMP Cysteine Development Diphtheria Toxin Disease Dose Drug Delivery Systems Drug Formulations Engineering Esters Goals Grooming Immune response Immunization Immunologist Inbred BALB C Mice Lead Lipids Liposomes Lysine Maleimides Malignant Neoplasms Methods Modeling Modification Molecular Monitor Mus Outcome Peptides Performance Phase Polysaccharides Precipitation Procedures Proteins Publishing Regulation Research Personnel Salmonella enterica Salmonella typhimurium Sampling Scaffolding Protein Series Serum Small Business Innovation Research Grant Solutions Surface System Technology Testing Typhoid Fever Typhoid Vaccine Vaccination Vaccines Vesicle Vi antigen Vi capsular polysaccharide Virus base commercialization cost cross reacting material 197 design engineering design flexibility fungus immunogenic interest meetings monophosphoryl lipid A mouse model mutant pathogen protective efficacy public health relevance response screening toll-like receptor 4 tool unilamellar vesicle vaccine candidate vaccine development

项目摘要

DESCRIPTION: In response to PA-10-150, we will test the hypothesis that the VesiVax(R) Conjugatable Adjuvant Lipid Vesicle (CALV) platform can provide an efficient method to develop carbohydrate conjugate vaccines that stimulates superior immune responses to unconjugated carbohydrate antigens and also provides more flexibility to control the immune response to carbohydrate antigens over currently employed conjugate vaccine technologies. To demonstrate the utility of the VesiVax(R) CALV platform for this purpose, we propose to develop a polysaccharide conjugation technology with the commercialization goal of producing an easy-to-use modification to the VesiVax(R) CALV line of products. It is anticipated that successful execution of this project will provide a new tool that will enable immunologists and vaccinologists to evaluate their carbohydrate antigens of interest. Polysaccharides are emerging as promising vaccine targets for a variety of pathogens including viruses, bacteria, fungi, and cancers. In this SBIR Phase I application, we will develop a simple carbohydrate conjugation method that couples polysaccharide antigens to free amines on either a protein scaffold or liposomes containing lipid amines. Specifically, using the capsular polysaccharide Vi from Salmonella enterica (typhi) as our model carbohydrate antigen, we will couple Vi directly to VesiVax(R) CALVs containing a Toll-like Receptor 4 (TLR4) agonist or to a protein scaffold based on the mutant of diphtheria toxin known as CRM197 engineered to have a C-terminal cysteine residue (CRM197-Cys). The Vi-CRM197-Cys will then be conjugated to the VesiVax(R) CALVs. The VesiVax(R) Vi CALV conjugates containing the TLR4 agonist will then be tested in a mouse model of immunization to demonstrate the utility of the proposed approach.

描述：对PA-10-150的响应，我们将检验以下假设：Vesivax（R）可结合的辅助脂质囊泡（CALV）平台可以提供一种有效的方法来开发碳水化合物偶联的疫苗，从而刺激刺激不受偶然的抗原抗凝结的抗凝结液，以刺激超级免疫反应，从而使碳水化合物的反应更高，以控制碳水化合物，以控制碳水化合物的抗原性，以控制碳水化合物的抗原性，以控制碳水化合物的降解性，以控制碳水化合物的反应，从而可以抗胆汁地降解。疫苗技术。为了为此目的展示Vesivax（R）CALV平台的实用性，我们建议开发多糖偶联技术，其商业化目标是为Vesivax（R）CALV产品生产易于使用的修改。预计该项目的成功执行将提供一种新工具，该工具将使免疫学家和疫苗科学家能够评估其感兴趣的碳水化合物抗原。多糖正在成为各种病原体的有希望的疫苗靶标，包括病毒，细菌，真菌和癌症。在此SBIR I期应用中，我们将开发一种简单的碳水化合物共轭方法，该方法将多糖抗原耦合在蛋白质支架或含有脂质胺的脂质体上释放胺。具体而言，将来自沙门氏菌（Typhi）的胶囊多糖VI作为我们的模型碳水化合物抗原，我们将直接将VI与vesivax（r）Calvs（r）Calvs（r）Calvs（calvs）（含有Toll样受体4（TLR4）激动剂或基于蛋白质的蛋白质crock的蛋白质或基于DIP-crinter的蛋白质crodanter crontante crontante crontant a dip crintar cym cym cym a残留物（CRM197-CYS）。然后，VI-CRM197-CYS将连接到Vesivax（R）CALV。然后将在免疫的小鼠模型中测试含有TLR4激动剂的vesivax（r）VI CALV结合物，以证明所提出的方法的实用性。