Data_Sheet_1_A Vaccinomics Approach for the Identification of Tick Protective Antigens for the Control of Ixodes ricinus and Dermacentor reticulatus Infestations in Companion Animals.xls

Ticks and tick-borne pathogens affect health and welfare of companion animals worldwide, and some human tick-borne diseases are associated with exposure to domestic animals. Vaccines are the most environmentally friendly alternative to acaracides for the control of tick infestations, and to reduce the risk for tick-borne diseases affecting human and animal health. However, vaccines have not been developed or successfully implemented for most vector-borne diseases. The main limitation for the development of effective vaccines is the identification of protective antigens. To address this limitation, in this study we used an experimental approach combining vaccinomics based on transcriptomics and proteomics data with vaccination trials for the identification of tick protective antigens. The study was focused on Ixodes ricinus and Dermacentor reticulatus that infest humans, companion animals and other domestic and wild animals, and transmit disease-causing pathogens. Tick larvae and adult salivary glands were selected for analysis to target tick organs and developmental stages playing a key role during tick life cycle and pathogen infection and transmission. Two I. ricinus (heme lipoprotein and uncharacterized secreted protein) and five D. reticulatus (glypican-like protein, secreted protein involved in homophilic cell adhesion, sulfate/anion exchanger, signal peptidase complex subunit 3, and uncharacterized secreted protein) proteins were identified as the most effective protective antigens based on the criteria of vaccine E > 80%. The putative function of selected protective antigens, which are involved in different biological processes, resulted in vaccines affecting multiple tick developmental stages. These results suggested that the combination of some of these antigens might be considered to increase vaccine efficacy through antigen synergy for the control of tick infestations and potentially affecting pathogen infection and transmission. These antigens were proposed for commercial vaccine development for the control of tick infestations in companion animals, and potentially in other hosts for these tick species.

蜱虫及蜱传病原体在全球范围内均可危害伴侣动物的健康与福利，且部分人类蜱传疾病的发生与接触家养动物存在关联。疫苗是替代杀蜱剂、防控蜱虫侵染，并降低影响人类与动物健康的蜱传疾病风险的最环保手段。然而，目前绝大多数虫媒传染病尚未开发出可成功应用的疫苗。有效疫苗研发的核心瓶颈在于保护性抗原的筛选与鉴定。为破解这一局限，本研究采用了整合式实验策略：将基于转录组学与蛋白质组学数据的疫苗组学研究与疫苗接种试验相结合，用于蜱虫保护性抗原的鉴定。本研究聚焦于蓖麻硬蜱（Ixodes ricinus）与网纹革蜱（Dermacentor reticulatus）——这两种蜱虫可侵染人类、伴侣动物及其他家养与野生动物，并传播致病病原体。研究选取蜱虫幼虫与成虫的唾液腺作为分析样本，靶向蜱虫生命周期、病原体侵染与传播过程中发挥关键作用的器官及发育阶段。基于疫苗保护效力E值＞80%的判定标准，共鉴定出2种蓖麻硬蜱蛋白（血红素脂蛋白、未表征分泌蛋白）与5种网纹革蜱蛋白（类磷脂酰肌醇蛋白聚糖、参与同型细胞黏附的分泌蛋白、硫酸盐/阴离子交换蛋白、信号肽酶复合物亚基3及未表征分泌蛋白）作为高效保护性抗原。所筛选的保护性抗原参与不同生物学过程，其潜在功能使得疫苗可作用于蜱虫的多个发育阶段。上述结果表明，可考虑联合使用部分此类抗原，通过抗原协同作用提升疫苗保护效力，以防控蜱虫侵染，并潜在阻断病原体的侵染与传播。本研究提出可针对上述抗原开发商用疫苗，用于防控伴侣动物的蜱虫侵染，同时也可潜在应用于该类蜱虫的其他宿主种群。