Genome-wide epitope mapping across multiple host species reveals significant diversity in antibody responses to Coxiella burnetii vaccination and infection.
Genome-wide epitope mapping across multiple host species reveals significant diversity in antibody responses to Coxiella burnetii vaccination and infection.
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DOI：
10.3389/fimmu.2023.1257722
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发表时间：
2023
影响因子：
7.3
通讯作者：
Mcneilly, Tom N.
中科院分区：
文献类型：
--
作者：
Bach, Emil;Fitzgerald, Stephen F.;Williams-MacDonald, Sarah E.;Mitchell, Mairi;Golde, William T.;Longbottom, David;Nisbet, Alasdair J.;Dinkla, Annemieke;Sullivan, Eric;Pinapati, Richard S.;Tan, John C.;Joosten, Leo A. B.;Roest, Hendrik-Jan;Osterbye, Thomas;Koets, Ad P.;Buus, Soren;Mcneilly, Tom N.
贝氏柯克斯体（Coxiellaburnetii）是一种重要的人畜共患细菌性病原体，可引起广泛的动物宿主Q热。反刍家畜，特别是绵羊和山羊，被认为是人类感染的主要宿主。疫苗接种是关键的控制措施，两种基于福尔马林灭活的C。贝氏藻毒素目前可用于家畜和人类。然而，由于在先前对C过敏的个体中具有显著的反应原性，因此它们的部署受到限制。贝氏体抗原此外，这些疫苗干扰了也是基于C. Burnetiiiuseinantigen.确定的亚单位抗原疫苗提供了显著的优势，因为它们可以被工程化以降低反应原性，并且与血清诊断测试共同设计以允许区分接种疫苗的个体和感染的个体。本研究的目的是探讨抗体反应的多样性，以C。通过全基因组线性表位作图来鉴定预测的细菌蛋白质组内的候选疫苗和诊断抗原，从而在牛、山羊、人和绵羊中检测贝氏体疫苗接种和/或感染。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份血清样品中对来自C.贝氏菌基因组我们发现，在物种内、物种间和不同类型的C.贝氏暴露通过实施三种不同的候选疫苗选择方法，我们确定了493个候选蛋白抗原的蛋白亚单位疫苗设计或血清学诊断评估，其中65个先前已被描述。这是第一个研究多个物种的血清反应性，对整个C。贝氏体蛋白质组呈现重叠的线性肽，并为下一代Q热疫苗和诊断测试的抗原靶标的选择提供了基础。
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.
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影响因子：
14.9
作者：
Gene Ontology Consortium
通讯作者：
Gene Ontology Consortium
DOI：
10.1016/j.xcrm.2021.100461
发表时间：
2021-12-21
期刊：
Cell reports. Medicine
影响因子：
--
作者：
Gregory AE;van Schaik EJ;Fratzke AP;Russell-Lodrigue KE;Farris CM;Samuel JE
通讯作者：
Samuel JE
影响因子：
5.2
作者：
Ruiz S;Wolfe DN
通讯作者：
Wolfe DN
影响因子：
3.7
作者：
Chen C;Dow C;Wang P;Sidney J;Read A;Harmsen A;Samuel JE;Peters B
通讯作者：
Peters B
影响因子：
3.7
作者：
Hansen CS;Østerbye T;Marcatili P;Lund O;Buus S;Nielsen M
通讯作者：
Nielsen M