Molecular Pharmaceutics and Drug Delivery, College of Pharmacy, The University of Texas, Austin, Texas, USA.
Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, Texas, USA.
Expert Rev Vaccines. 2021 May;20(5):623-634. doi: 10.1080/14760584.2021.1899818. Epub 2021 Mar 18.
Infectious disease emergencies like the 2013-2016 Ebola epidemic and the 2009 influenza and current SARS-CoV-2 pandemics illustrate that vaccines are now given to diverse populations with preexisting pathologies requiring pharmacological management. Many natural biomolecules (steroid hormones, fatty acids, vitamins) and ~60% of prescribed medications are processed by hepatic cytochrome P450 (CYP) 3A4. The objective of this work was to determine the impact of infection and vaccines on drug metabolism.
The impact of an adenovirus-based vaccine expressing Ebola glycoprotein (AdEBO) and H1N1 and H3N2 influenza viruses on hepatic CYP 3A4 and associated nuclear receptors was evaluated in human hepatocytes (HC-04 cells) and in mice.
CYP3A activity was suppressed by 55% in mice 24 h after administration of mouse-adapted H1N1, while ˂10% activity remained in HC-04 cells after infection with H1N1 and H3N2 due to global suppression of cellular translation capacity, indicated by reduction (70%, H1N1, 56%, H3N2) of phosphorylated eukaryotic translation initiation factor 4e (eIF4E). AdEBO suppressed CYP3A activity (44%) and (26%) 24 hours after infection.
As the clinical evaluation of vaccines for SARS-CoV-2 and other global pathogens rise, studies to evaluate the impact of new vaccines and emerging pathogens on CYP3A4 and other metabolic enzymes are warranted to avoid therapeutic failures that could further compromise the public health during infectious disease emergencies.
2013-2016 年埃博拉疫情、2009 年流感和当前的 SARS-CoV-2 大流行等传染病突发事件表明，现在为具有需要药物治疗的先前存在的病理的不同人群接种疫苗。许多天然生物分子（甾体激素、脂肪酸、维生素）和~60%的处方药都是由肝细胞色素 P450（CYP）3A4 处理的。本研究的目的是确定感染和疫苗对药物代谢的影响。
用表达埃博拉糖蛋白（AdEBO）和 H1N1、H3N2 流感病毒的腺病毒疫苗在人原代肝细胞（HC-04 细胞）和小鼠中评估对肝 CYP3A4 和相关核受体的影响。
在接受适应小鼠的 H1N1 疫苗后 24 小时，小鼠的 CYP3A 活性降低了 55%，而在感染 H1N1 和 H3N2 后，HC-04 细胞中仅残留~10%的活性，这是由于细胞翻译能力的全面抑制，通过降低磷酸化真核起始因子 4e（eIF4E）（H1N1 为 70%，H3N2 为 56%）来指示。AdEBO 在感染后 24 小时分别抑制 CYP3A 活性（44%）和（26%）。
随着对 SARS-CoV-2 和其他全球病原体疫苗的临床评估增加，有必要评估新疫苗和新出现的病原体对 CYP3A4 和其他代谢酶的影响，以避免治疗失败，这可能在传染病突发事件期间进一步损害公共健康。
