000075814 001__ 75814
000075814 005__ 20191212102145.0
000075814 0247_ $$2doi$$a10.3389/fimmu.2018.02406
000075814 0248_ $$2sideral$$a108407
000075814 037__ $$aART-2018-108407
000075814 041__ $$aeng
000075814 100__ $$aVarela-Martinez, E.
000075814 245__ $$aMolecular Signature of Aluminum Hydroxide Adjuvant in Ovine PBMCs by Integrated mRNA and microRNA Transcriptome Sequencing
000075814 260__ $$c2018
000075814 5060_ $$aAccess copy available to the general public$$fUnrestricted
000075814 5203_ $$aThere have been few in vivo studies on the effect of aluminum hydroxide adjuvant and its influence on the immune response to vaccination. In this study, lambs received a parallel subcutaneous treatment with either commercial vaccines containing aluminum hydroxide or an equivalent dose of this compound only with the aim of identifying the activated molecular signature. Blood samples were taken from each animal at the beginning and at the end of the experiment and PBMCs isolated. Total RNA and miRNA libraries were prepared and sequenced. After alignment to the Oar3.1 reference genome and differential expression with 3 programs, gene enrichment modeling was performed. For miRNAs, miRBase and RNAcentral databases were used for detection and characterization. Three expression comparisons were made: vaccinated animals at the beginning and at the end of the treatment, adjuvanted animals at the same times, and animals of both treatments at the end of the experiment. After exposure to both treatments, a total of 2, 473; 2, 980 and 429 differentially expressed genes were identified in vaccinated animals, adjuvanted animals and animals at the end of both treatments, respectively. In both adjuvant and vaccine treated animals the NF-kappa B signaling pathway was enriched. On the other hand, it can be observed a downregulation of cytokines and cytokine receptors in the adjuvanted group compared to the vaccinated group at the final time, suggesting a milder induction of the immune response when the adjuvant is alone. As for the miRNA analysis, 95 miRNAs were detected: 64 previously annotated in Ovis aries, 11 annotated in Bos taurus and 20 newly described. Interestingly, 6 miRNAs were differentially expressed in adjuvant treated animals, and 3 and 1 in the other two comparisons. Lastly, an integrated miRNA-mRNA expression profile was developed, in which a miRNA-mediated regulation of genes related to DNA damage stimulus was observed. In brief, it seems that aluminum-containing adjuvants are not simple delivery vehicles for antigens, but also induce endogenous danger signals that can stimulate the immune system. Whether this contributes to long-lasting immune activation or to the overstimulation of the immune system remains to be elucidated.
000075814 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000075814 590__ $$a4.716$$b2018
000075814 591__ $$aIMMUNOLOGY$$b42 / 157 = 0.268$$c2018$$dQ2$$eT1
000075814 592__ $$a2.021$$b2018
000075814 593__ $$aImmunology and Allergy$$c2018$$dQ1
000075814 593__ $$aImmunology$$c2018$$dQ1
000075814 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000075814 700__ $$aAbendano, N.
000075814 700__ $$0(orcid)0000-0002-6178-4801$$aAsin, J.$$uUniversidad de Zaragoza
000075814 700__ $$aSistiaga-Poveda, M.
000075814 700__ $$aPerez, M.M.
000075814 700__ $$aReina, R.
000075814 700__ $$ade Andres, D.
000075814 700__ $$0(orcid)0000-0002-2053-9842$$aLujan, L.$$uUniversidad de Zaragoza
000075814 700__ $$aJugo, B.M.
000075814 7102_ $$11009$$2773$$aUniversidad de Zaragoza$$bDpto. Patología Animal$$cÁrea Sanidad Animal
000075814 773__ $$g9 (2018), 2406 [16 pp]$$pFront. immunol.$$tFrontiers in Immunology$$x1664-3224
000075814 8564_ $$s612689$$uhttps://zaguan.unizar.es/record/75814/files/texto_completo.pdf$$yVersión publicada
000075814 8564_ $$s11429$$uhttps://zaguan.unizar.es/record/75814/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000075814 909CO $$ooai:zaguan.unizar.es:75814$$particulos$$pdriver
000075814 951__ $$a2019-12-12-10:14:32
000075814 980__ $$aARTICLE