Development of O Antigen-based Vaccines Against Q Fever

描述（由申请方提供）：贝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。它是一种未充分研究的B类选择性病原体，可以通过气溶胶传播，因此，创造一种安全有效的疫苗来预防Q热仍然是一个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的细胞内细菌病原体的安全，有效的疫苗。本申请的目的是鉴定C.贝氏I相脂多糖（PI-LPS），其可赋予对雾化C.伯内特氏菌为了达到这一目的，我们将检验中心假设，即C。贝氏体PI-LPS是赋予针对Q热的保护性免疫的关键抗原。本研究的目的是证明PI-LPS的O抗原保护性表位的肽模拟物可以赋予针对C.贝氏体感染该方案有两个具体目的：目的1：确定PI-LPS的O抗原是否是关键的保护性抗原。我们将确定是否有抗C的O抗原抗体。Burnetii PI-LPS具有保护性，并鉴定了可提供针对C.贝氏体感染我们还将确定从PI-LPS纯化的O抗原是否可以提供针对C的保护。贝氏体感染目的2：鉴定具有抗C.贝氏体感染我们将确定肽模拟物，可以赋予保护性免疫，对C。贝氏疟原虫感染，并确定O抗原的保护性表位的肽模拟物是否可以引发针对C.贝氏体感染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C的保护。贝氏体感染作为本研究的一个结果，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C.贝氏体感染这将对人类健康产生重大的积极影响，因为它将为Q热疫苗的设计提供信息，并反过来导致开发新的策略来干扰其他危险的细胞内细菌病原体的气溶胶传播。

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.