Abstract
Aluminium hydroxide adjuvants are crucial for livestock and human vaccines. Few studies have analysed their effect on the central nervous system in vivo. In this work, lambs received three different treatments of parallel subcutaneous inoculations during 16 months with aluminium-containing commercial vaccines, an equivalent dose of aluminium hydroxide or mock injections. Brain samples were sequenced by RNA-seq and miRNA-seq for the expression analysis of mRNAs, long non-coding RNAs and microRNAs and three expression comparisons were made. Although few differentially expressed genes were identified, some dysregulated genes by aluminium hydroxide alone were linked to neurological functions, the lncRNA TUNA among them, or were enriched in mitochondrial energy metabolism related functions. In the same way, the miRNA expression was mainly disrupted by the adjuvant alone treatment. Some differentially expressed miRNAs had been previously linked to neurological diseases, oxidative stress and apoptosis. In brief, in this study aluminium hydroxide alone altered the transcriptome of the encephalon to a higher degree than commercial vaccines that present a milder effect. The expression changes in the animals inoculated with aluminium hydroxide suggest mitochondrial disfunction. Further research is needed to elucidate to which extent these changes could have pathological consequences.
Highlights
Aluminium hydroxide adjuvants are crucial for livestock and human vaccines
In relation to the conservation of the detected long non-coding RNAs (lncRNAs) in sheep, we identified few lncRNAs already annotated in other species through Blast searches against RNAcentral; among them, the lncRNA TUNA was detected, which was differentially expressed between the adjuvant group and the other two groups
Three comparisons were made with the transcriptomes: Adjuvant inoculated vs. controls, vaccinated vs. controls and adjuvant inoculated vs. vaccinated animals
Summary
Aluminium hydroxide adjuvants are crucial for livestock and human vaccines. Few studies have analysed their effect on the central nervous system in vivo. Few differentially expressed genes were identified, some dysregulated genes by aluminium hydroxide alone were linked to neurological functions, the lncRNA TUNA among them, or were enriched in mitochondrial energy metabolism related functions. The expression changes in the animals inoculated with aluminium hydroxide suggest mitochondrial disfunction. Since the 1920’s, when aluminium (Al) was discovered to enhance immune response providing more effective protection[1] vaccines have been complemented with adjuvants. Because of the effectiveness of aluminium adjuvants at enhancing humoral responses, their good tolerance without causing fever and with the longest safety record among used a djuvants[2] aluminium salts are preferably used in both animal and human vaccines. In CD1 mice, with a dose of 100 μg Al/kg, subcutaneously inoculated Alhydrogel adjuvant induced cognitive alterations associated with death of motor neurons and an enormous increase (350%) of reactive astrocytic cells in an inflammatory process[4]. In the mechanisms associated with Al neurotoxicity and that aberrant mRNAs and lncRNAs were involved in the response to Al in the analysed tissue
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