Development and Evaluation of a Dual-Antigen Nasal Brucella Vaccine

双抗原鼻布鲁氏菌疫苗的开发与评价

基本信息

批准号：
7531644
负责人：
Yongqun He
金额：
$ 20.69万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-07-21 至 2011-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7531644
关键词：
Adjuvant Aerosols Affect Animal Model Animals Antibodies Antigens Attenuated Bacteria Biological Biological Warfare Bioterrorism Brucella Brucella Vaccine Brucella abortus Brucella melitensis Brucellosis Categories Cellular Immunity Centers for Disease Control and Prevention (U.S.)Cuprozinc Superoxide Dismutase Cytotoxic T-Lymphocytes DNA Development Dose Drug Formulations Engineering Escherichia coli Evaluation Foundations Future Gastrointestinal tract structure Goals Goat HIV Antigens HIV vaccine Human IgG1 Immune response Immunity Immunization Inbred BALB C Mice Infection Injection of therapeutic agent Interleukin-12 Interleukin-2 Interleukin-4 Lipopolysaccharides Liposomes Lung Membrane Methods Mucosal Immunity Mucous Membrane Mus Names National Institute of Allergy and Infectious Disease National Security Nose Population Proteins Public Health RNA Recombinants Respiratory System Respiratory tract structure Route Sampling Serum Sheep Skin Spleen Superoxide Dismutase Surface T-Lymphocyte Terrorism Th1 Cells Vaccinated Vaccination Vaccine Adjuvant Vaccine Antigen Vaccines Virulent abstracting base cell mediated immune response human SOD2 protein improved lipopolysaccharide B mortality mouse model novel novel vaccines overexpression pathogen prototype public health relevance response sound vaccine candidate vaccine development vaccine efficacy weapons

项目摘要

DESCRIPTION (provided by applicant): Abstract: Facultative intracellular Brucella species cause brucellosis in animals and humans and have been classified as NIAID category B priority pathogens. Brucella infects the body via the respiratory tract, the skin, and the digestive tract. There is no Brucella vaccine available for human use. Thus, novel vaccines that are non-infectious to humans but effective in stimulating a broad protective immune response are needed. A nasal vaccine that induces both systemic and mucosal immunities would be ideal. Purified smooth Brucella lipopolysaccharide (LPS) induces protection against virulent Brucella infections in different animal models. Brucella LPS is also much less toxic than that from E. coli and has been used as a vaccine adjuvant to facilitate the induction of HIV antigen specific cell-mediated immune response. Additionally, Brucella Cu/Zn Superoxide Dismutase (SOD) is a protective antigen that induces significant protection against brucellosis when combined with IL-2, overexpressed in a Brucella vaccine, or expressed in DNA or RNA vaccines. We hypothesize that a dual-antigen Brucella vaccine containing both LPS and Cu/Zn SOD, when dosed intranasally with appropriate adjuvant(s), will induce significant levels of LPS- and Cu/Zn SOD-specific Th1 and cell mediated immunity to protect against virulent Brucella infection. The overall goal of this proposal is 1) to develop a dual antigen Brucella vaccine by conjugating B. melitensis LPS and Cu/Zn SOD (LPS-SOD) and 2) to evaluate the immune responses induced when nasally dosed with appropriate adjuvants in a well-established mouse model. This project is expected to generate a novel prototype nasal Brucella vaccine candidate and lay a sound scientific foundation for the development of an efficacious nasal Brucella vaccine for human use. PUBLIC HEALTH RELEVANCE: Brucella species cause debilitating brucellosis in humans and animals and have been listed as pathogens potentially used for bioterrorism. However, there is no Brucella vaccine available for human use. This proposal aims to develop and analyze a novel prototype nasal Brucella vaccine by conjugating two protective Brucella antigens.

描述（由申请人提供）：摘要：兼性细胞内布鲁氏菌属引起动物和人类布鲁氏菌病，已被列为 NIAID B 类优先病原体。布鲁氏菌通过呼吸道、皮肤和消化道感染人体。目前还没有可供人类使用的布鲁氏菌疫苗。因此，需要对人类无传染性但能有效刺激广泛的保护性免疫反应的新型疫苗。诱导全身和粘膜免疫的鼻疫苗将是理想的。纯化的平滑布鲁氏菌脂多糖 (LPS) 可在不同的动物模型中诱导防止致命的布鲁氏菌感染。布鲁氏菌脂多糖的毒性也比大肠杆菌低得多，并已被用作疫苗佐剂，以促进诱导艾滋病毒抗原特异性细胞介导的免疫反应。此外，布鲁氏菌铜/锌超氧化物歧化酶 (SOD) 是一种保护性抗原，当与在布鲁氏菌疫苗中过表达或在 DNA 或 RNA 疫苗中表达的 IL-2 结合时，可诱导针对布鲁氏菌病的显着保护。我们假设含有 LPS 和 Cu/Zn SOD 的双抗原布鲁氏菌疫苗，当与适当的佐剂一起鼻内给药时，将诱导显着水平的 LPS 和 Cu/Zn SOD 特异性 Th1 和细胞介导的免疫，以预防致命的布鲁氏菌感染。该提案的总体目标是 1) 通过结合羊种布鲁氏菌 LPS 和铜/锌 SOD (LPS-SOD) 来开发双抗原布鲁氏菌疫苗，2) 评估在孔中用适当佐剂经鼻给药时诱导的免疫反应-建立小鼠模型。该项目预计将产生一种新型鼻用布鲁氏菌候选疫苗原型，并为开发人用有效的鼻用布鲁氏菌疫苗奠定良好的科学基础。公共卫生相关性：布鲁氏菌属会导致人类和动物衰弱的布鲁氏菌病，并已被列为可能用于生物恐怖主义的病原体。然而，目前还没有可供人类使用的布鲁氏菌疫苗。该提案旨在通过结合两种保护性布鲁氏菌抗原来开发和分析一种新型鼻布鲁氏菌疫苗原型。