Different protective efficacies of a novel antigen-specific DNA vaccine encoding chicken type Ⅱ collagen via intramuscular, subcutaneous, and intravenous vaccination against experimental rheumatoid arthritis.

Abstract

Tolerizing DNA vaccines encoding key autoantigens are one of emerging strategies for the treatment of rheumatoid arthritis (RA). Among these vaccines, the most representative is pcDNA-CCOL2A1, an antigen-specific DNA vaccine encoding chicken type Ⅱ collagen (CCⅡ) with significant therapeutic and prophylactic efficacy in collagen-induced arthritis (CIA) rat models. We compared the in situ expression levels of CCOL2A1-mRNA and CCⅡ protein and the protective efficacies against CIA after a single dose (300 μg/kg) of this vaccine via intramuscular (IM), subcutaneous (SC) and intravenous (IV) vaccinations. The IM vaccination routes resulted in good protective efficacies in terms of decreasing CIA incidence and severity and significantly improved radiographic and histopathologic findings and scores of joints. Furthermore, IM, SC, and IV vaccinations markedly decreased serum levels of anti-type Ⅱ collagen (CⅡ) IgG antibodies, but only IM vaccination significantly reduced serum levels of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibody. The vaccine exhibited a continuous CCOL2A1-mRNA expression in the tail and abdominal subcutaneous tissue injection sites, but no CCOL2A1-mRNA signal was observed in muscle. Strikingly, CCⅡ protein expression levels at the three injection sites were comparable with minimal variation. IM administration may be considered the preferred route for RA treatment in clinical practice.

• Authors: Xiao Zhao, Juan Long, Fei Liang, Nan Liu, Yuying Sun, Yongzhi Xi
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 144 Pg. 112294 (Dec 2021) ISSN: 1950-6007 [Electronic] France
• PMID: 34653764 (Publication Type: Comparative Study, Journal Article)
• Copyright: Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Chemical References

• Autoantibodies
• COL2A1 protein, rat
• Collagen Type II
• Vaccines, DNA

Topics

• Animals
• Arthritis, Experimental (blood, diagnostic imaging, immunology, prevention & control)
• Arthritis, Rheumatoid (blood, immunology, pathology, prevention & control)
• Autoantibodies (blood)
• Collagen Type II (administration & dosage, genetics, immunology)
• Female
• Injections, Intramuscular
• Injections, Intravenous
• Injections, Subcutaneous
• Joints (diagnostic imaging, drug effects, immunology, metabolism)
• Rats, Wistar
• Time Factors
• Vaccination
• Vaccine Efficacy
• Vaccines, DNA (administration & dosage, genetics, immunology)
• Rats