首页> 美国卫生研究院文献>Frontiers in Cellular and Infection Microbiology >Vaccinomics Approach to the Identification of Candidate Protective Antigens for the Control of Tick Vector Infestations and Anaplasma phagocytophilum Infection
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Vaccinomics Approach to the Identification of Candidate Protective Antigens for the Control of Tick Vector Infestations and Anaplasma phagocytophilum Infection

机译:疫苗组学方法用于识别控制T虫侵染和吞噬嗜浆细胞感染的候选保护性抗原

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摘要

Anaplasma phagocytophilum is an emerging tick-borne pathogen causing human granulocytic anaplasmosis (HGA), tick-borne fever (TBF) in small ruminants, and other forms of anaplasmosis in different domestic and wild animals. The main vectors of this pathogen are Ixodes tick species, particularly I. scapularis in the United States and I. ricinus in Europe. One of the main limitations for the development of effective vaccines for the prevention and control of A. phagocytophilum infection and transmission is the identification of effective tick protective antigens. The objective of this study was to apply a vaccinomics approach to I. scapularis-A. phagocytophilum interactions for the identification and characterization of candidate tick protective antigens for the control of vector infestations and A. phagocytophilum infection. The vaccinomics pipeline included the use of quantitative transcriptomics and proteomics data from uninfected and A. phagocytophilum-infected I. scapularis ticks for the selection of candidate protective antigens based on the variation in tick mRNA and protein levels in response to infection, their putative biological function, and the effect of antibodies against these proteins on tick cell apoptosis and pathogen infection. The characterization of selected candidate tick protective antigens included the identification and characterization of I. ricinus homologs, functional characterization by different methodologies including RNA interference, immunofluorescence, gene expression profiling, and artificial tick feeding on rabbit antibodies against the recombinant antigens to select the candidates for vaccination trials. The vaccinomics pipeline developed in this study resulted in the identification of two candidate tick protective antigens that could be selected for future vaccination trials. The results showed that I. scapularis lipocalin (ISCW005600) and lectin pathway inhibitor () and I. ricinus homologs constitute candidate protective antigens for the control of vector infestations and A. phagocytophilum infection. Both antigens are involved in the tick evasion of host defense response and pathogen infection and transmission, but targeting different immune response pathways. The vaccinomics pipeline proposed here could be used to continue the identification and characterization of candidate tick protective antigens for the development of effective vaccines for the prevention and control of HGA, TBF, and other forms of anaplasmosis caused by A. phagocytophilum.
机译:吞噬性无浆细胞是一种新兴的由tick传播的病原体,可引起人类反刍动物的粒细胞无性菌病(HGA),tick传热(TBF),以及其他家养和野生动物中的其他形式的无性病。该病原体的主要媒介是I虱(Ixodes tick),尤其是美国的肩鱼和欧洲的蓖麻(I. ricinus)。开发用于预防和控制噬菌体感染和传播的有效疫苗的主要限制之一是鉴定有效的壁虱保护性抗原。这项研究的目的是将免疫组学方法应用于肩capI。噬菌体相互作用,用于鉴定和表征候选壁虱保护性抗原,以控制载体侵染和噬菌体感染。疫苗经济学渠道包括使用来自未感染和嗜A.噬菌体感染的肩I小tick的定量转录组学和蛋白质组学数据,根据tick对感染的tick mRNA和蛋白水平变化,推定的生物学功能,选择候选保护性抗原。以及针对这些蛋白质的抗体对on细胞凋亡和病原体感染的影响。选定的候选壁虱保护性抗原的表征包括蓖麻一菌的鉴定和表征,通过不同方法的功能表征,包括RNA干扰,免疫荧光,基因表达谱分析以及人工抗取食针对重组抗原的兔抗体以选择候选的抗原疫苗接种试验。在这项研究中开发的疫苗经济学渠道导致鉴定出两种候选的tick保护性抗原,这些抗原可以选择用于未来的疫苗接种试验。结果表明,肩脂肪脂蛋白(ISCW005600)和凝集素途径抑制剂()和蓖麻毒素同源物构成了候选的保护性抗原,可用于控制病媒和吞噬嗜血杆菌的感染。两种抗原都参与宿主防御反应和病原体感染和传播的the虫回避,但靶向不同的免疫反应途径。此处提出的疫苗经济学渠道可用于继续鉴定和表征候选tick保护性抗原,以开发预防和控制HGA,TBF和其他形式的吞噬链球菌引起的无性体质病的有效疫苗。

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