Tick feeding or vaccination with tick antigens elicits immunity to the Ixodes scapularis exoproteome in guinea pigs and humans

IF 14.6 1区 医学 Q1 CELL BIOLOGY Science Translational Medicine Pub Date : 2025-03-26 DOI:10.1126/scitranslmed.ads9207
Thomas M. Hart, Yingjun Cui, Sam R. Telford, Alejandro Marín-López, Keith Calloway, Yile Dai, Jaqueline Matias, Kathleen DePonte, Jillian Jaycox, Melody DeBlasio, Dieuwertje Hoornstra, Alexia A. Belperron, Balasubramanian Cibichakravarthy, Emily E. Johnson, Mohamad-Gabriel Alameh, Garima Dwivedi, Joppe W. R. Hovius, Linda K. Bockenstedt, Drew Weissman, Aaron M. Ring, Erol Fikrig
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Abstract

Ixodes scapularis is a primary vector of tick-borne pathogens in North America. Repeated exposure to these ticks can induce a humoral response to tick antigens and acquired tick resistance. However, identifying antigens contributing to this resistance is challenging because of the vast number of I. scapularis proteins secreted during feeding. To address this, we developed I. scapularis rapid extracellular antigen monitoring (IscREAM), a technique to detect antibody responses to more than 3000 tick antigens. We validated IscREAM with immunoglobulin G (IgG) from guinea pigs vaccinated with tick antigens, including a cement antigen cocktail that induced tick resistance. Furthermore, we explored the natural response to tick bites by profiling antigens recognized by IgG isolated from a tick-resistant individual, as well as from others with Lyme disease and tick-bitten guinea pigs and mice, to identify 199 recognized antigens. We observed that several antigens contained histamine-binding domains. This work enhances our understanding of the host immune response to I. scapularis and defines immunogen candidates for future antitick vaccines.
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在豚鼠和人类中,蜱虫喂养或接种蜱虫抗原可引起对肩胛硬蜱外蛋白组的免疫
肩胛硬蜱是北美洲蜱传病原体的主要媒介。反复接触这些蜱虫可以诱导对蜱虫抗原的体液反应,并获得蜱虫抗性。然而,由于在摄食过程中分泌了大量的肩胛棘球绦虫蛋白,因此鉴定导致这种抗性的抗原是具有挑战性的。为了解决这个问题,我们开发了肩胛骨蜱快速细胞外抗原监测(Isc REAM),一种检测3000多种蜱抗原抗体反应的技术。我们用免疫球蛋白G (IgG)验证了Isc REAM,这些IgG来自接种了蜱虫抗原的豚鼠,包括一种诱导蜱虫抗性的水泥抗原鸡尾酒。此外,我们通过分析从抗蜱个体、莱姆病患者、被蜱叮咬的豚鼠和小鼠中分离的IgG所识别的抗原来探索蜱叮咬的自然反应,鉴定出199种识别抗原。我们观察到一些抗原含有组胺结合结构域。这项工作增强了我们对肩胛棘球蚴的宿主免疫反应的理解,并确定了未来抗蜱疫苗的候选免疫原。
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来源期刊
Science Translational Medicine
Science Translational Medicine CELL BIOLOGY-MEDICINE, RESEARCH & EXPERIMENTAL
CiteScore
26.70
自引率
1.20%
发文量
309
审稿时长
1.7 months
期刊介绍: Science Translational Medicine is an online journal that focuses on publishing research at the intersection of science, engineering, and medicine. The goal of the journal is to promote human health by providing a platform for researchers from various disciplines to communicate their latest advancements in biomedical, translational, and clinical research. The journal aims to address the slow translation of scientific knowledge into effective treatments and health measures. It publishes articles that fill the knowledge gaps between preclinical research and medical applications, with a focus on accelerating the translation of knowledge into new ways of preventing, diagnosing, and treating human diseases. The scope of Science Translational Medicine includes various areas such as cardiovascular disease, immunology/vaccines, metabolism/diabetes/obesity, neuroscience/neurology/psychiatry, cancer, infectious diseases, policy, behavior, bioengineering, chemical genomics/drug discovery, imaging, applied physical sciences, medical nanotechnology, drug delivery, biomarkers, gene therapy/regenerative medicine, toxicology and pharmacokinetics, data mining, cell culture, animal and human studies, medical informatics, and other interdisciplinary approaches to medicine. The target audience of the journal includes researchers and management in academia, government, and the biotechnology and pharmaceutical industries. It is also relevant to physician scientists, regulators, policy makers, investors, business developers, and funding agencies.
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