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）：伯氏柯克斯体是一种专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。它是一种正在研究中的 B 类选择病原体，可以通过气溶胶传播，因此开发安全有效的疫苗来预防 Q 热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方法来发现针对气溶胶传播的细胞内细菌病原体的安全、有效的疫苗。本申请的目的是确定伯内特衣原体 I 相脂多糖 (PI-LPS) 上的表位，这是实现这一目标的重要一步，该表位可以提供针对雾化伯内特衣原体肺部感染的保护。为了实现这一目标，我们将检验以下中心假设：伯氏念珠菌 PI-LPS 的 O 抗原是赋予针对 Q 热的保护性免疫力的关键抗原。本提案的目的是证明 PI-LPS O 抗原上的保护性表位的肽模拟物可以赋予针对伯纳特衣原体感染的保护性免疫。该提案有两个具体目标： 目标 1：确定 PI-LPS 的 O 抗原是否是关键的保护性抗原。我们将确定针对伯纳特衣原体 PI-LPS 的 O 抗原的抗体是否具有保护性，并鉴定可提供针对伯纳特衣原体感染的保护的单克隆抗体 (mAb)。我们还将确定从 PI-LPS 中纯化的 O 抗原是否可以提供针对伯氏念珠菌感染的保护作用。目标 2：鉴定能够赋予伯氏念珠菌感染保护性免疫力的肽模拟物。我们将鉴定能够赋予针对伯纳特衣原体感染的保护性免疫的肽模拟物，并确定O抗原保护性表位的肽模拟物是否能够引发针对伯纳特衣原体感染的保护性免疫。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针对伯内特念珠菌感染的保护。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拟物可以引发针对伯纳特衣原体感染的保护性免疫。这将对人类健康产生显着的积极影响，因为它将为针对 Q 热的疫苗设计提供信息，进而导致开发新策略来干扰其他危险的细胞内细菌病原体的气溶胶传播。