Mining a differential sialotranscriptome of Rhipicephalus microplus guides antigen discovery to formulate a vaccine that reduces tick infestations
Mining a differential sialotranscriptome of Rhipicephalus microplus guides antigen discovery to formulate a vaccine that reduces tick infestations
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DOI：
10.1186/s13071-017-2136-2
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发表时间：
2017-04-26
影响因子：
3.2
通讯作者：
de Miranda-Santos, Isabel K. F.
中科院分区：
文献类型：
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作者：
Maruyama, Sandra R.;Garcia, Gustavo R.;de Miranda-Santos, Isabel K. F.
背景资料：蜱虫对牲畜造成巨大损害，疫苗是目前大量用于控制虫害的杀螨剂的可持续替代品。为了指导针对蜱唾液介导的各种寄生策略并实现免疫记忆的疫苗的抗原发现，我们利用了从喂食遗传抗蜱和易感牛的微小扇头蜱的所有阶段的唾液腺构建的转录组。因此，我们选择了由在试图以抗性宿主为食的蜱中弱表达或在以易感宿主为食的蜱中丰富表达的基因编码的四种蛋白质;这些唾液蛋白介导由雄性蜱部署的寄生的四种功能，并且在自然感染的易感牛中不诱导抗体。然后，我们在蜱敏感的小母牛中评估了用重组蛋白配制的明矾佐剂疫苗。寄生虫表现在接种与对照小母牛中，抗原特异性抗体的滴度（即完成其寄生周期的雌性的重量和数量）和滴度分别显著降低或增加，赋予73.2%的效力;其中两种抗原是强免疫原，富含预测的T细胞表位，并且攻击侵染增强了针对它们的抗体应答。由抗蜱宿主的免疫力指导的唾液转录组挖掘选择了重要的靶标，并且感染增强了对唾液抗原的免疫记忆。
Background: Ticks cause massive damage to livestock and vaccines are one sustainable substitute for the acaricides currently heavily used to control infestations. To guide antigen discovery for a vaccine that targets the gamut of parasitic strategies mediated by tick saliva and enables immunological memory, we exploited a transcriptome constructed from salivary glands from all stages of Rhipicephalus microplus ticks feeding on genetically tick-resistant and susceptible bovines.Results: Different levels of host anti-tick immunity affected gene expression in tick salivary glands; we thus selected four proteins encoded by genes weakly expressed in ticks attempting to feed on resistant hosts or otherwise abundantly expressed in ticks fed on susceptible hosts; these sialoproteins mediate four functions of parasitism deployed by male ticks and that do not induce antibodies in naturally infected, susceptible bovines. We then evaluated in tick-susceptible heifers an alum-adjuvanted vaccine formulated with recombinant proteins. Parasite performance (i.e. weight and numbers of females finishing their parasitic cycle) and titres of antigen-specific antibodies were significantly reduced or increased, respectively, in vaccinated versus control heifers, conferring an efficacy of 73.2%; two of the antigens were strong immunogens, rich in predicted T-cell epitopes and challenge infestations boosted antibody responses against them.Conclusion: Mining sialotranscriptomes guided by the immunity of tick-resistant hosts selected important targets and infestations boosted immune memory against salivary antigens.