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挖掘微小扇头蜱的差异唾液转录组可指导抗原发现,以研制出一种能减少蜱虫侵袭的疫苗。

Mining a differential sialotranscriptome of Rhipicephalus microplus guides antigen discovery to formulate a vaccine that reduces tick infestations.

作者信息

Maruyama Sandra R, Garcia Gustavo R, Teixeira Felipe R, Brandão Lucinda G, Anderson Jennifer M, Ribeiro José M C, Valenzuela Jesus G, Horackova Jana, Veríssimo Cecília J, Katiki Luciana M, Banin Tamy M, Zangirolamo Amanda F, Gardinassi Luiz G, Ferreira Beatriz R, de Miranda-Santos Isabel K F

机构信息

Departament of Biochemistry and Immunology, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, SP, 14049-900, Brazil.

Department of Genetics and Evolution, Federal University of São Carlos, São Carlos, SP, 13565-905, Brazil.

出版信息

Parasit Vectors. 2017 Apr 26;10(1):206. doi: 10.1186/s13071-017-2136-2.

Abstract

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.

摘要

背景

蜱虫对家畜造成巨大损害,疫苗是目前大量用于控制蜱虫侵扰的杀螨剂的一种可持续替代品。为了指导针对蜱虫唾液介导的一系列寄生策略并能产生免疫记忆的疫苗的抗原发现,我们利用了从微小牛蜱各发育阶段唾液腺构建的转录组,这些蜱虫以具有抗蜱基因和易感的牛为宿主进行取食。

结果

不同水平的宿主抗蜱免疫影响蜱虫唾液腺中的基因表达;因此,我们选择了四种蛋白质,它们由在试图取食抗性宿主的蜱虫中弱表达或以其他方式在取食易感宿主的蜱虫中大量表达的基因编码;这些唾液蛋白介导雄蜱虫的四种寄生功能,且在自然感染的易感牛中不会诱导抗体产生。然后,我们在易感蜱虫的小母牛中评估了一种用重组蛋白配制的明矾佐剂疫苗。与对照小母牛相比,接种疫苗的小母牛的寄生虫表现(即完成寄生周期的雌蜱重量和数量)和抗原特异性抗体滴度分别显著降低或升高,疫苗效力达73.2%;其中两种抗原是强免疫原,富含预测的T细胞表位,再次感染会增强针对它们的抗体反应。

结论

以抗蜱宿主的免疫力为指导挖掘唾液转录组,可选择重要靶点,再次感染可增强对唾液抗原的免疫记忆。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf8e/5406933/b440e6f745b3/13071_2017_2136_Fig1_HTML.jpg

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