Vaccine Development for Burkholderia amllei and B. pseudomallei

鼻疽伯克霍尔德杆菌和类鼻疽伯克霍尔德杆菌的疫苗开发

基本信息

批准号：
8233017
负责人：
Don MARK ESTES
金额：
$ 47.96万
依托单位：
UNIVERSITY OF TEXAS MED BR GALVESTON
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-03-01 至 2014-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8233017
关键词：
Acute Disease Adjuvant Aerosols Animal Disease Models Animals Antibiotics Antibody Formation Antigens Attenuated Vaccines Bacteria Biological Biological Markers Biological Warfare Burkholderia Burkholderia Infections Burkholderia mallei Burkholderia pseudomallei Carrier Proteins Categories Cells Characteristics Chemicals Child Code Conjugate Vaccines Containment Controlled Study Coupling Data Set Development Disease Disease model Dolphins Dose Drug Formulations Elderly Environment Evaluation Flagella Flagellin Generations Genetic Genome Glanders Glycoconjugates Goals Gram-Negative Bacteria Haemophilus influenzae Host resistance Human Immune Immune Sera Immune response Immunity Immunocompromised Host Immunoglobulin M Individual Infection Laboratory mice Licensing Licensure Link Lipopolysaccharides Macaca Malleus Mediating Medical Melioidosis Methods Modeling Mus Neisseria meningitidis Non obese O Antigens Organism Pharmaceutical Preparations Polysaccharides Population Pregnant Women Process Production Proteins Publishing Recombinant Proteins Recombinants Reporting Resources Route Safety Salmonella typhi Severe Combined Immunodeficiency Streptococcus pneumoniae Study Section Subunit Vaccines Surface System T-Lymphocyte Technology Texas United States Food and Drug Administration Universities Vaccines Virulence Factors Whole Cell Vaccine Work austin base biodefense candidate selection capsule cell killing cell mediated immune response combat comparative efficacy cost cost effective diabetic diabetic rat genome sequencing genome-wide humanized SCID mouse immunogenic immunogenicity induced pluripotent stem cell killings microorganism named group nonhuman primate pathogen prophylactic response safety study vaccine candidate vaccine delivery vaccine development weapons

项目摘要

This proposal is directed towards the development of vaccines for the category B agents Burkholderia pseudomallei and Burkholderia mallei. There is an urgent and acknowledged need to develop better Drophylactic countermeasures through the use of vaccines and immune stimulants for both melioidosis and glanders. We believe it is appropriate to consider these pathogens in parallel in this project because they are closely related at a genetic level, and there is a possibility that common approaches to these diseases can be identified. The aims of this project are to: (1) Identify optimal delivery systems and protein carriers. (2) Develop optimized protein-polysaccharide conjugation methods. (3) Compare efficacy of homologous versus heterologous protein-polysaccharide conjugates. (4) Identify biomarkers and mechanisms of vaccine-mediated protection in acute disease models, including the laboratory mouse, the humanized SCID mouse, and nonhuman primate models. Our principal aim is to devise a non-living vaccine which is able to protect against both 6. pseudomallei and 8. mallei infection. This is an important consideration for eventual licensure and use with potential applications for special populations such as young children, the elderly, pregnant women and immunocompromised subjects. Ultimately, the studies outlined in this proposal will establish a data set to begin the process of a successful submission of an investigative new drug (IND) application to the Food and Drug Administration.

该提案旨在开发针对 B 类病原体伯克霍尔德杆菌的疫苗鼻疽和鼻疽伯克霍尔德氏菌。迫切需要更好地发展通过使用疫苗和免疫刺激剂来预防类鼻疽和类鼻疽鼻疽。我们认为在这个项目中并行考虑这些病原体是适当的，因为它们是在基因水平上密切相关，并且治疗这些疾病的共同方法有可能可以被识别。该项目的目标是： (1) 确定最佳的递送系统和蛋白质载体。 (2)开发优化的蛋白质-多糖缀合方法。 (3) 比较同源与异源蛋白质-多糖缀合物的功效。 (4) 确定急性疾病模型中疫苗介导的保护的生物标志物和机制，包括实验室小鼠、人源化 SCID 小鼠和非人灵长类动物模型。我们的主要目标是设计一种能够预防 6. 假鼻疽的非活疫苗 8.鼻疽感染。这是最终许可和潜在使用的重要考虑因素针对幼儿、老人、孕妇等特殊人群的申请免疫功能低下的受试者。最终，本提案中概述的研究将建立一个数据集开始向食品和药物管理局成功提交新药研究 (IND) 申请的流程药品管理局。