Development of O Antigen-based Vaccines Against Q Fever

基于 O 抗原的 Q 热疫苗的开发

• 批准号: 8386914
• 负责人: Guoquan Zhang
• 金额: $ 35.01万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-12-01 至 2015-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8386914
• 关键词: Acute; Adjuvant; Aerosols; Antibodies; Antigen Targeting; Antigens; Biohazardous Substance; Biological Warfare; Bioterrorism; Breathing; Categories; Cavia; Cellular Immunity; Chronic; Coxiella burnetii; Development; Disease; Doctor of Philosophy; Epitopes; Goals; Gram-Negative Bacteria; Health; Human; Immune response; Immunity; Immunoglobulin G; Immunology; Infection; Laboratories; Lead; Libraries; Lipopolysaccharides; Lung; Mediating; Missouri; Modeling; Monoclonal Antibodies; Mus; Nature; O Antigens; Organism; Outcomes Research; Passive Transfer of Immunity; Pathogenesis; Peptides; Phage Display; Phase; Pneumonia; Polysaccharides; Principal Investigator; Proteins; Public Health; Q Fever; Qualifying; Role; Route; Safety; Serial Passage; Serum; System; Testing; Universities; Vaccinated; Vaccine Design; Vaccines; Variant; Virulent; Work; aerosolized; base; biosecurity; egg; experience; innovation; novel; novel strategies; pathogen; polyclonal antibody; prevent; programs; public health relevance; screening; tissue culture; transmission process; vaccine candidate

DESCRIPTION (provided by applicant): Coxiella burnetii is an obligate intracellular gram-negative bacterium that causes acute Q fever and chronic infections in humans. It is an understudied category B select agent and can be transmitted via aerosol, thus creation of a safe and effective vaccine to prevent Q fever remains an important public health and national biosecurity goal. The long-term goal of this program is to develop new approaches to discover safe, effective vaccines against aerosol-transmitted intracellular bacterial pathogens. The objective of this application, which is an essential step towards this goal, is to identify the epitopes on C. burnetii phase I lipopolysaccharide (PI-LPS) that can confer protection against pulmonary infection with aerosolized C. burnetii. To achieve this objective, we will test the central hypothesis that O antigen of C. burnetii PI-LPS is the key antigen to confer protective immunity against Q fever. The purpose of this proposal is to prove the concept that peptide mimics of protective epitopes on O antigen of PI-LPS can confer protective immunity against C. burnetii infection. The proposal has two specific aims: Aim 1: to determine if O antigen of PI-LPS is the key protective antigen. We will determine if Ab against O antigen of C. burnetii PI-LPS is protective and identify the monoclonal antibodies (mAbs) that can provide protection against C. burnetii infection. We will also determine if purified O antigen from PI-LPS can confer protection against C. burnetii infection. Aim 2: to identify the peptide mimics that can confer protective immunity against C. burnetii infection. We will identify the peptide mimics that can confer protective immunity against C. burnetii infection and determine if peptide mimics of protective epitopes of O antigen can elicit protective immunity against C. burnetii infection. We will also determine if chemically synthesized peptide mimics, in the context of an adjuvant and a suitable delivery system, can provide protection against C. burnetii infection. As an outcome of this research, we expect to prove the concept that peptide mimics of protective epitopes of O antigen can elicit protective immunity against C. burnetii infection. This would have significant positive effects on human health, because it would provide information for vaccine design against Q fever, and in turn lead to development of new strategies to interfere with aerosol transmission of other dangerous intracellular bacterial pathogens.

描述（由申请人提供）：Coxiella burnetii是一种强制性细胞内革兰氏阴性细菌，可引起人类急性Q热和慢性感染。它是B类精选剂的研究，可以通过气溶胶传输，因此创建安全有效的疫苗以防止Q发烧，仍然是重要的公共卫生和国家生物安全目标。该计划的长期目标是开发新的方法，以发现针对气溶胶传播细胞内细菌病原体的安全有效疫苗。该应用的目的是朝着这一目标迈出的重要一步，是确定C. burnetii I期脂多糖（PI-LPS）上的表位，该表位可以允许用烟熏C. burnetii提供保护肺部感染的保护。为了实现这一目标，我们将测试中心假设：burnetii pi-lps的O抗原是赋予抗Q发烧保护性免疫力的关键抗原。该提议的目的是证明肽对Pi-LPS抗原的保护性表位的肽模仿可以赋予保护性免疫，以抵抗burnetii C. burnetii感染。该提案具有两个具体的目的：目标1：确定PI-LPS的O抗原是否是关键保护性抗原。我们将确定针对burnetii pi-lps的O抗原的AB是否具有保护性，并鉴定可以提供保护抗牛梭菌感染的单克隆抗体（mAb）。我们还将确定PI-LPS中纯化的O抗原是否可以允许防止弯曲梭菌感染。目标2：确定可以赋予抗牛梭菌感染的保护性免疫的肽模拟物。我们将确定肽模拟物可以赋予抗牛梭菌感染的保护性免疫，并确定O抗原的保护性表位的肽模拟物是否会引起对伯内特菌感染的保护性免疫。我们还将确定化学合成的肽模拟物在佐剂和合适的递送系统的背景下是否可以提供防止伯内蒂感染的保护。作为这项研究的结果，我们期望证明O抗原保护性表位的肽模仿可以引起对伯内特梭菌感染的保护性免疫。这将对人类健康产生重大的积极影响，因为它将为疫苗设计提供针对Q热的疫苗设计的信息，进而导致开发新策略，以干扰其他危险的细胞内细菌病原体的气溶胶传播。