DNA Vaccines for Q fever

Q 热 DNA 疫苗

• 批准号: 7675560
• 负责人: David W Pascual
• 金额: $ 18.81万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7675560
• 关键词: Address; Adjuvant; Adverse reactions; Aerosols; Animals; Antibiotic Therapy; Antibodies; Bacteria; Brucellosis; Categories; Cavia; Coxiella; Coxiella burnetii; DNA Vaccines; Dairy Products; Development; Disease; Drug Formulations; Exposure to; Food; Formalin; Gram-Negative Bacteria; Human; Immunity; Ingestion; Livestock; Lung; Lung diseases; Mediating; Mucosal Immunity; Mus; Nose; Phagolysosome; Phase; Proteins; Q Fever; Recombinant Proteins; Research; Research Project Grants; Resources; Route; Subunit Vaccines; System; TLR2 gene; Testing; Treatment Protocols; Vaccinated; Vaccination; Vaccine Adjuvant; Vaccines; Virulent; biodefense; communicable disease diagnosis; efficacy testing; flu; immunoregulation; microorganism; novel vaccines; pathogen; research study; success; vaccine candidate; vaccine delivery

Q fever is an understudied and under diagnosed infectious disease caused by the Category B agent, Coxiella burnetii. C. burnetii is a highly infectious Gram-negative bacterium causing disease with as few as 1 - 10 microorganisms. Q fever is naturally transmitted via ingestion of unpasteurized dairy products or by exposure to infected aerosols, manifesting disease with flu-like systems, and despite antibiotic treatment, the success of the treatment is not guaranteed. Q-Vax, formalin-inactivated whole bacteria, is currently the only human vaccine used for Q fever, but not approved in the US. Pre-exposure to C. burnetii can result in adverse reactions to Q-Vax. Given these impediments, a need exists to develop an efficacious, preferably subunit vaccine that minimizes such reactivities. Protection to Q fever appears to be both antibody- and cellmediated immunity-dependent, with the expression of TLR2 and IFN-y being important for mediating protective immunity. In the previous application, efforts focused on identifying C. burnetii proteins that enable its survival in the host phagolysosome as vaccine candidates. This approach has been successfully used in selecting similar vaccine candidates for brucellosis. Using this approach, 5-8 new vaccine candidates have been identified and vaccination with the collective recombinant proteins confers protective immunity against C. burnetii Nine Mile phase I challenge. To forward this effort, studies in Specific Aim 1 will optimize the vaccine formulation by testing different adjuvants and routes of delivery to optimize protective immunity that induces IFN-y and confers protective immunity. Studies in Specific Aim 2 will adapt these vaccines to our nasal delivery platform to enhance mucosal immunity to protect against pulmonary challenge. Studies in Specific Aim 3 will test the efficacy of these candidates against pulmonary challenge in both mice and guinea pigs. Phase I C. burnetii will be provided by Core B, the Coxiella Core; interactions will occur with Project 1.2 for Th1 and Th17 adjuvant discovery and Project 1.1 for optimizing pulmonary immunity to C. burnetii. We hypothesize that we can derive <8 candidates that can be formulated for eventual development of a Q fever vaccine. This research project fits within the RMRCE Integrated Research Focus on Immunomodulation, Adjuvants, and Vaccines, and will interact with RP 1.1 and RP 1.2 and utilize the resources of Coxiella Core.

Q热是一种由B类病原体引起的未得到充分研究和诊断的传染病， 伯氏柯克斯体。伯氏梭菌是一种传染性很强的革兰氏阴性细菌，只有1种 -10个微生物。Q热是通过摄入未经巴氏灭菌的乳制品或通过 暴露在受感染的气雾剂中，表现为流感样系统的疾病，尽管接受了抗生素治疗，但 治疗的成功并不能保证。Q-VAX，福尔马林灭活的完整细菌，是目前唯一 用于Q热的人类疫苗，但在美国未获批准。预先接触伯氏梭菌可导致 Q-VAX的不良反应。鉴于这些障碍，有必要制定一种有效的、最好是 将这种反应性降至最低的亚单位疫苗。对Q热的保护似乎既是抗体介导的，也是细胞介导的 免疫依赖性，TLR2和干扰素-γ的表达是重要的中介作用 保护豁免权。在之前的申请中，工作重点是鉴定布氏梭菌蛋白， 使其作为候选疫苗在宿主吞噬酶体内存活。这种方法已经成功地实现了 用于选择类似的布鲁氏菌病候选疫苗。使用这种方法，5-8种新疫苗 候选者已经确定，用集体重组蛋白接种疫苗具有保护作用 对伯氏梭菌的免疫力九英里第一阶段挑战。为了推进这一努力，具体目标1的研究将 通过测试不同的佐剂和递送途径来优化疫苗配方，以优化保护 诱导干扰素-γ并提供保护性免疫的免疫。在特定目标2中的研究将适应这些 疫苗到我们的鼻腔递送平台，增强黏膜免疫力，预防肺炎 挑战。针对特定目标3的研究将测试这些候选者对抗肺挑战的有效性 无论是老鼠还是豚鼠。第一阶段C.Burnetii将由Coxiella Core B提供； 将与用于Th1和Th17佐剂发现的项目1.2以及用于优化肺组织的项目1.1一起进行 对伯氏梭菌有免疫力。我们假设我们可以推导出可以用公式表示的8个候选者 最终研制出Q热疫苗。本研究项目适用于RMRCE集成 研究重点是免疫调节、佐剂和疫苗，并将与RP 1.1和RP 1.2相互作用 和利用柯克斯氏菌核心的资源。