Dynamic profiles, biodistribution and integration evaluation after intramuscular/intravenous delivery of a novel therapeutic DNA vaccine encoding chicken type II collagen for rheumatoid arthritis in vaccinated normal rodent

Journal of Nanobiotechnology

Fei Liang¹  Yongzhi Xi¹  Xiao Zhao¹  Juan Long¹  Nan Liu¹  Yuying Sun¹ 

[1]Department of Immunology and National Center for Biomedicine Analysis, the Fifth Medical Center (formerly known as Beijing 307 Hospital), Chinese PLA General Hospital

关键词: Therapeutic DNA vaccine;    Dynamic profiles;    Biodistribution;    Genomic integration;    Rheumatoid arthritis;   

DOI  :  10.1186/s12951-019-0528-5

来源: DOAJ

【 摘 要 】

Abstract Background The persistence, biodistribution, and risk of integration into the host genome of any new therapeutic DNA vaccine must be established in preclinical studies. We previously developed the DNA vaccine pcDNA-CCOL2A1 encoding chicken type II collagen (CCII) for the treatment of rheumatoid arthritis (RA). In the present study, we characterized its dynamic profile, biodistribution, and potential for genomic DNA integration in normal vaccinated rodent. Results A real-time quantitative PCR analysis (RT-qPCR) of animals administered a single dose of pcDNA-CCOL2A1 (300 μg/kg by intramuscular injection) showed that CCOL2A1 mRNA level in the blood peaked between 2 and 6 h post-immunization and then rapidly declined, and was undetectable between day 1–42. CCOL2A1 transcript was detected at the muscle injection site on days 3–14 post-immunization. Starting from day 14, the transcript was detected in the heart, liver, lung, and kidney but not in the spleen or thymus, and was expressed only in the lung on day 28. There was no CCOL2A1 mRNA present in the testes or ovaries at any time point. Non-invasive in vivo fluorescence imaging revealed CCII protein expression from 2 h up to day 10 and from 2 h up to day 35 after administration of pcDNA-CCOL2A1 via the intravenous and intramuscular routes, respectively; the protein had disappeared by day 42. Importantly, CCOL2A1 was not integrated into the host genome. Conclusions These results indicate that pcDNA-CCOL2A1 vaccine is rapidly cleared within a short period of time and is therefore safe, and merits further development as a therapeutic vaccine for RA treatment.

【 授权许可】

Unknown