Evaluation of Rat Acute Phase Proteins as Inflammatory Biomarkers for Vaccine Nonclinical Safety Studies
| Autor: | Rani S. Sellers, Ahmed M. Shoieb, Shelli J. Schomaker, William J. Reagan, David W. Clarke, Victoria Markiewicz |
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| Rok vydání: | 2020 |
| Předmět: |
Lipopolysaccharide
Whooping Cough medicine.medical_treatment Pharmacology Toxicology Fibrinogen Pathology and Forensic Medicine 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Animals 030212 general & internal medicine Rats Wistar Molecular Biology 030304 developmental biology Diphtheria toxin 0303 health sciences Tetanus Chemistry Acute-phase protein Toxoid Cell Biology Rats Macroglobulin Female Lymph Adjuvant Biomarkers Acute-Phase Proteins medicine.drug |
| Zdroj: | Toxicologic Pathology. 48:845-856 |
| ISSN: | 1533-1601 0192-6233 |
| DOI: | 10.1177/0192623320957281 |
| Popis: | The objectives were to characterize the kinetics of acute phase proteins (APPs) α-2 macroglobulin (A2M), α-1 acid glycoprotein (A1AGP), and fibrinogen (FIB), and injection site macroscopic and microscopic findings following intramuscular administration of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (TDaP; Adacel); adjuvants (aluminum phosphate [AlPO4]; aluminum hydroxide, Al[OH]3; CpG/Al[OH]3; or Quillaja saponaria 21 [QS-21]); or saline to female Wistar Han rats. Intravascular lipopolysaccharide (LPS) was a positive control. Injection sites and lymph nodes were evaluated microscopically, using hematoxylin and eosin (H&E) stained sections, 48 hours postdose (HPD) and compared with APP concentrations; A2M and A1AGP were measured using Meso Scale Discovery analyzer. Fibrinogen was measured on STA Compact analyzer. In a time-course study, APP peaked at 24 or 48 HPD. In a subsequent study at 48 HPD, injection site microscopic changes included inflammation and muscle degeneration/necrosis, which was different in severity/nature between groups. The APPs were not increased in rats administered saline, Al(OH)3, or AlPO4. Fibrinogen and A1AGP increased in rats administered CpG/Al(OH)3, QS-21, or TDaP; and A2M increased in rats administered QS-21. Fibrinogen, A2M, and A1AGP increased after LPS administration. Acute phase proteins can be used to monitor inflammatory responses to adjuvants; however, some adjuvants may induce inflammation without higher APPs. |
| Databáze: | OpenAIRE |
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