Blocking interleukin-4 enhances efficacy of vaccines for treatment of opioid abuse and prevention of opioid overdose.
Blocking interleukin-4 enhances efficacy of vaccines for treatment of opioid abuse and prevention of opioid overdose.
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DOI：
10.1038/s41598-018-23777-6
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发表时间：
2018-04-03
影响因子：
4.6
通讯作者：
Pravetoni M
中科院分区：
文献类型：
--
作者：
Laudenbach M;Baruffaldi F;Robinson C;Carter P;Seelig D;Baehr C;Pravetoni M
疫苗为治疗海洛因和处方阿片类药物滥用和预防致命的过量用药提供了一种选择。阿片样物质疫苗引发抗体，阻断阿片样物质向大脑的分布，减少阿片样物质引起的行为效应和毒性。成瘾疫苗转化的主要限制是，只有在达到最佳药物特异性血清抗体水平的受试者中才能观察到疗效。本研究测试了免疫调节剂靶向参与B细胞和T细胞淋巴细胞活化的关键细胞因子信号通路是否能提高抗氧可酮疫苗的效力。阻断IL-4信号通路可提高疫苗阻断羟考酮向大脑分布的效力，并可保护小鼠免受阿片类药物诱导的行为和毒性。这种策略推广到肽-蛋白结合免疫原和破伤风-白喉-百日咳疫苗。这些数据表明，基于细胞因子的免疫调节剂提高了疫苗对小分子、多肽和蛋白质的效力，并确定了IL-4作为提高下一代疫苗效力的药理学靶点。
Vaccines offer an option to treat heroin and prescription opioid abuse and prevent fatal overdoses. Opioid vaccines elicit antibodies that block opioid distribution to the brain and reduce opioid-induced behavioral effects and toxicity. The major limitation to the translation of addiction vaccines is that efficacy is observed only in subjects achieving optimal drug-specific serum antibody levels. This study tested whether efficacy of a vaccine against oxycodone is increased by immunomodulators targeting key cytokine signaling pathways involved in B and T cell lymphocyte activation. Blockage of IL-4 signaling increased vaccine efficacy in blocking oxycodone distribution to the brain and protection against opioid-induced behavior and toxicity in mice. This strategy generalized to a peptide-protein conjugate immunogen, and a tetanus-diphtheria-pertussis vaccine. These data demonstrate that cytokine-based immunomodulators increase efficacy of vaccines against small molecules, peptides and proteins, and identify IL-4 as a pharmacological target for improving efficacy of next-generation vaccines.
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