Immunization and Drug Metabolizing Enzymes: Focus on Hepatic Cytochrome P450 3A.
Expert Rev Vaccines
; 20(5): 623-634, 2021 05.
Article
in English
| MEDLINE | ID: covidwho-1118865
ABSTRACT
OBJECTIVE:
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.METHODS:
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.RESULTS:
CYP3A activity was suppressed by 55% in mice 24 h after administration of mouse-adapted H1N1, while Ë10% 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 in vivo (44%) and in vitro (26%) 24 hours after infection.CONCLUSION:
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.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Pharmaceutical Preparations
/
Hepatocytes
/
Cytochrome P-450 CYP3A
/
Liver
Type of study:
Experimental Studies
/
Prognostic study
Topics:
Vaccines
Limits:
Animals
/
Humans
/
Male
Language:
English
Journal:
Expert Rev Vaccines
Journal subject:
Allergy and Immunology
Year:
2021
Document Type:
Article
Affiliation country:
14760584.2021.1899818
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