伯氏菌是一种重要的人畜共患细菌病原体,具有全球重要性,在广泛的动物宿主中引起疾病Q热。反刍动物,尤其是绵羊和山羊,被认为是人类感染的主要来源。疫苗接种是一项关键的控制措施,和两种基于福尔马林灭活的伯氏梭菌菌苗的商业疫苗目前可用于牲畜和人类。然而,由于先前对伯氏梭菌抗原敏感的个体的显著反应原性,它们的部署受到限制.此外,这些疫苗会干扰可用的血清诊断测试,这些测试也基于伯氏芽孢杆菌菌素抗原。定义亚单位抗原疫苗具有显著的优势,因为它们可以被设计为降低反应原性,并与血清诊断测试共同设计,以允许在接种疫苗和感染个体之间进行区分。本研究旨在调查牛对C.burnetii疫苗接种和/或感染的抗体反应的多样性。山羊,人类,和绵羊通过全基因组线性表位作图,在预测的细菌蛋白质组中鉴定候选疫苗和诊断抗原。使用高密度肽微阵列,我们分析了来自接种疫苗和感染个体的156份血清样品中来自C.burnetii基因组中2,092个开放阅读框的肽的血清反应性。我们发现物种内部和物种之间以及不同类型的C.burnetii暴露之间的抗体反应存在显着差异。通过实施三种不同的候选疫苗选择方法,我们确定了493个候选蛋白抗原,用于蛋白亚单位疫苗设计或血清诊断评估,其中65个之前已经描述过。这是第一项研究针对以重叠线性肽形式呈现的整个C.burnetii蛋白质组的多物种血清反应性的研究,并为下一代Q发烧疫苗和诊断测试的抗原靶标选择提供了基础。
Coxiella burnetii is an important zoonotic bacterial pathogen of global importance, causing the disease Q fever in a wide range of animal hosts. Ruminant livestock, in particular sheep and goats, are considered the main reservoir of human infection. Vaccination is a key control measure, and two commercial vaccines based on formalin-inactivated C. burnetii bacterins are currently available for use in livestock and humans. However, their deployment is limited due to significant reactogenicity in individuals previously sensitized to C. burnetii antigens. Furthermore, these vaccines interfere with available serodiagnostic tests which are also based on C. burnetii bacterin antigens. Defined subunit antigen vaccines offer significant advantages, as they can be engineered to reduce reactogenicity and co-designed with serodiagnostic tests to allow discrimination between vaccinated and infected individuals. This study aimed to investigate the diversity of antibody responses to C. burnetii vaccination and/or infection in cattle, goats, humans, and sheep through genome-wide linear epitope mapping to identify candidate vaccine and diagnostic antigens within the predicted bacterial proteome. Using high-density peptide microarrays, we analyzed the seroreactivity in 156 serum samples from vaccinated and infected individuals to peptides derived from 2,092 open-reading frames in the C. burnetii genome. We found significant diversity in the antibody responses within and between species and across different types of C. burnetii exposure. Through the implementation of three different vaccine candidate selection methods, we identified 493 candidate protein antigens for protein subunit vaccine design or serodiagnostic evaluation, of which 65 have been previously described. This is the first study to investigate multi-species seroreactivity against the entire C. burnetii proteome presented as overlapping linear peptides and provides the basis for the selection of antigen targets for next-generation Q fever vaccines and diagnostic tests.