Glanders Vaccine Developement

鼻疽疫苗开发

基本信息

批准号：
7449961
负责人：
Donald E. WOODS
金额：
$ 35.92万
依托单位：
UNIVERSITY OF CALGARY
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-07-01 至 2012-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7449961
关键词：
Abscess Accounting Acellular Vaccines Acute Aerosols Afghanistan Africa Alcoholism Ally American Civil War American Type Culture Collection Animal Diseases Animal Feed Animal Model Animals Antibiotic Resistance Antibodies Antibody Formation Antigens Appearance Area Asia Asses Attenuated Attenuated Live Virus Vaccine Australia Bacillus (bacterium)Bacteremia Bacteria Bacterial Adhesins Bacterial Infections Belief Biological Biological Assay Biological Warfare Bioterrorism Blast Cell Blood Circulation Body Weight decreased Branched-Chain Amino Acids Breathing Brucella melitensis Burkholderia Burkholderia mallei Burkholderia pseudomallei Burn injury CD4 Positive T Lymphocytes Camels Canis familiaris Carrier Proteins Case Study Categories Cattle Cavia Cells Centers for Disease Control and Prevention (U.S.)Cessation of life Chemicals China Chromosomes Chromosomes, Human, Pair 1 Chromosomes, Human, Pair 2 Chronic Chronic lung disease Cirrhosis Classification Clinical Communicable Diseases Communities Conjugate Vaccines Consumption Country Cutaneous Cystic Fibrosis DCNU DNA Insertion Elements Deletion Mutation Development Diabetes Mellitus Diagnosis Diarrhea Disaccharides Disease Disease Association Disease Progression Disease remission Disruption Egypt Emerging Communicable Diseases Environment Epithelial Cells Equine mule Equus caballus Evolution Exhibits Exotoxins Experimental Models Failure Family Farming environment Fatigue Felis catus Fever Flagellin Focal Infection France Francisella tularensis Future Genes Genetic Engineering Genomics Genus Capra German population Germany Glanders Glycerol Goat Granuloma Guanine + Cytosine Composition Hamsters Hand Headache Helper-Inducer T-Lymphocyte Hong Kong Hospitals Human IS Elements Immune response Immune system Immunity Immunization Immunotherapeutic agent Inbred BALB C Mice Incidence Individual Infection Institutes Intervention Island Japanese Population Kava Knowledge Laboratories Laboratory Animals Laboratory culture Lead Left Life Lipopolysaccharides Liquid substance Listeria monocytogenes Livestock Localized Lung Lymph Lymphadenitis Lymphangitis Lymphatic vessel Malleus Manchuria Mediating Medical Melioidosis Membrane Membrane Proteins Metabolic Middle East Military Personnel Modeling Molecular Morbidity - disease rate Movement Mucous Membrane Mucous body substance Mus Mutagenesis Mutation Myalgia Mycobacterium tuberculosis Names Nature Needles Neisseria Northern Territory Nose Nucleic Acids Nucleotides Numbers O Antigens Oceans Oils Open Reading Frames Organ Organism Oryctolagus cuniculus Passive Immunity Pathogenesis Pathology Patients Personal Satisfaction Phase Plasmids Play Pneumonia Poland Polysaccharides Positioning Attribute Preparation Prevention Prevention approach Principal Investigator Prisoner Probability Protein translocation Proteins Protocols documentation Public Health Publishing Purines Pus Range Recombinants Recording of previous events Relative (related person)Reporting Research Personnel Rice Risk Risk Factors Rodent Rodent Model Role Romania Route Rural Russia Salmonella Salmonella typhi Seasons Septicemia Serological Serum Shigella Shipping Ships Site Skin Soft Tissue Infections Soldier South Australia Southeastern Asia Staging Sterility Structure Study Section Subunit Vaccines Suicide Surface Surface Antigens Surveys Symptoms System Testing Thailand Thalassemia Thinking Time Travel Tuberculosis USSR Ulcer United States Urea Vaccinated Vaccination Vaccines Variant Vietnam Virulence Virulence Factors Virulent War Wood material World War I World War II Yersinia Yersinia pestis Youth base capsule cell mediated immune response cell preparation day disorder control experience extracellular human disease immunogenic immunoprophylaxis immunosuppressed improved interest irritation latent infection lymph nodes man member mortality mouse model mutant optimism pathogen prevent programs purine research study respiratory success temperature sensitive mutant tool transmission process transposon/insertion element vaccine development

项目摘要

DESCRIPTION (provided by applicant): Our broad, long-term objectives are to develop human vaccines for the prevention of glanders caused by Burkholderia mallei, and for melioidosis caused by B. pseudomallei. In the currently proposed studies, we will examine the immune response to B. mallei and B. pseudomallei vaccine candidates in small animals and in the horse, and we will determine the efficacy of immunotherapeutic interventions in challenge studies with an aim toward developing plans for extending the results to a human vaccine. The major hypothesis being evaluated is that immunotherapeutic intervention is a viable approach for the prevention of glanders caused by B. mallei and for the prevention of melioidosis caused by the closely related organism, B. pseudomallei. We have made significant progress in the last number of years in the identification of the virulence determinants of B. mallei and B. pseudomallei which we hypothesize will be excellent candidates as components of conjugate vaccines. Of particular note are two polysaccharide structures present on the surface of both of these organisms which are critical for the virulence of both of these. These are an extracellular polysaccharide capsule (CPS) and lipopolysaccharide O-antigen (OPS). We propose to conjugate the CPS and OPS polysaccharides to six carrier proteins shown or predicted to play important roles in pathogenesis by B. pseudomallei and B. mallei. CPS and OPS will also be conjugated to recombinant exotoxin A, a proven efficacious carrier protein of polysaccharide-based vaccines. We believe that this strategy will identify a vaccine that will protect against B. mallei challenge in a mouse model of infection as well as against B. mallei challenge in the horse which is the natural host for the organism. If shown to be successful in preventing glanders, this vaccine will be subsequently used in human trials to investigate protection against melioidosis in Australia and Thailand. Our specific aims are: 1. To evaluate the immune response to CPS and OPS conjugated to the carrier proteins in mice and in the horse. 2. To determine the ability of CPS and OPS conjugated to the carrier proteins to protect against B. mallei challenge in a BALB/c mouse model of infection. 3. To test the hypothesis that CPS and OPS conjugates which are protective in BALB/c mice will also protect the horse against B. mallei challenge. We believe that immunotherapeutic intervention is a viable approach for the prevention of glanders caused by B. mallei and for the prevention of melioidosis caused by the closely related organism, B. pseudomallei. Since B. mallei and B. pseudomallei are of significance as agents of bioterrorism (Category B, Centers for Disease Control, U.S.) and biological warfare, the development of effective vaccines are of particular concern. Vaccines will also have considerable multi-use potential since the diseases caused by these organisms are recognized as emerging infectious diseases in various areas of the world.

描述（由申请人提供）：我们广泛的长期目标是开发人类疫苗，用于预防鼻疽伯克霍尔德氏菌引起的鼻疽和类鼻疽伯克霍尔德氏菌引起的类鼻疽。在目前提出的研究中，我们将检查小动物和马对鼻疽伯克氏菌和拟鼻疽伯克氏菌候选疫苗的免疫反应，并且我们将确定挑战研究中免疫治疗干预措施的功效，旨在制定延长计划人类疫苗的结果。正在评估的主要假设是，免疫治疗干预是预防鼻疽伯克霍尔德引起的鼻疽和预防密切相关的类鼻疽生物引起的类鼻疽的可行方法。过去几年，我们在鉴定鼻疽伯克霍尔德氏菌和类鼻疽伯克氏菌的毒力决定因素方面取得了重大进展，我们假设它们将成为结合疫苗成分的优秀候选者。特别值得注意的是这两种生物体表面存在两种多糖结构，这对于这两种生物体的毒力至关重要。它们是细胞外多糖胶囊 (CPS) 和脂多糖 O 抗原 (OPS)。我们建议将 CPS 和 OPS 多糖与六种载体蛋白缀合，这些载体蛋白已显示或预测在类鼻疽伯克氏菌和鼻疽伯克氏菌的发病机制中发挥重要作用。 CPS 和 OPS 还将与重组外毒素 A 结合，重组外毒素 A 是一种经过验证的有效多糖疫苗载体蛋白。我们相信，这一策略将鉴定出一种疫苗，既可以防止小鼠感染模型中的鼻疽杆菌攻击，也可以防止作为该生物体的天然宿主的马中的鼻疽杆菌攻击。如果证明能成功预防鼻疽，该疫苗随后将用于人体试验，以研究澳大利亚和泰国对类鼻疽的预防作用。我们的具体目标是： 1. 评估小鼠和马对与载体蛋白缀合的 CPS 和 OPS 的免疫反应。 2. 确定与载体蛋白缀合的 CPS 和 OPS 在 BALB/c 小鼠感染模型中抵御鼻疽杆菌攻击的能力。 3. 检验以下假设：对 BALB/c 小鼠具有保护作用的 CPS 和 OPS 缀合物也能保护马免受鼻疽杆菌的攻击。我们相信，免疫治疗干预是预防鼻疽伯克霍尔德引起的鼻疽和预防密切相关的类鼻疽生物引起的类鼻疽的可行方法。由于鼻疽伯克氏菌和伪鼻疽伯克氏菌作为生物恐怖主义（美国疾病控制中心 B 类）和生物战的重要媒介，因此有效疫苗的开发受到特别关注。由于这些生物体引起的疾病在世界各地被认为是新出现的传染病，因此疫苗也将具有相当大的多用途潜力。