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

Tolerizing DNA vaccines encoding key autoantigens are one of emerging strategies for the treatment of rheu-matoid 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 mu g/kg) of this vaccine via intra-muscular (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.