Evaluation of humoral and cellular immune responses to a DNA vaccine encoding chicken type II collagen for rheumatoid arthritis in normal rats

Zhao, Xia; Liu, Juan; Song, Yun S.; Zhang, Zhijian; Jin, Jing; Kun, Yu; Yuna, Hao; Dongfa, Dai; Ding, Lili; Liuxin, Tan; Liang, Fei; Liu, Nan; Yuan, Fang; Sun, Yawang; Yang, Xi

doi:10.1080/21645515.2015.1010977

Cited by 11 publications

(6 citation statements)

References 28 publications

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“…We recently reported that vaccination with pcDNA- CCOL2A1 at a dose of 3 mg/kg was well-tolerated by rats [11]. The optimal therapeutic dose of 300 μg/kg did not induce production of anti-CII IgG and did not alter the expression levels of most cytokines and T-lymphocyte subsets in normal rats [10], suggesting that pcDNA- CCOL2A1 is a promising therapeutic DNA vaccine with high druggability. We therefore evaluated the dynamic profiles of pcDNA- CCOL2A1 in rats at the same dose by assessing clearance after vaccination.…”

Section: Resultsmentioning

confidence: 99%

“…Based on these valuable findings, we previously developed the pcDNA- CCOL2A1 therapeutic vaccine encoding CCII and found that its efficacy was comparable to that of the current gold standard drug methotrexate (MTX) in a rat model of collagen-induced arthritis (CIA) [9]. More recently, we showed that pcDNA- CCOL2A1 was safe and well-tolerated as a therapeutic vaccine, did not markedly affect the balance of humoral and cellular immune responses, and had no immunogenicity in normal rats when administered by intramuscular injection [10, 11]. Integrated all research evidence from our studies strongly suggest that pcDNA- CCOL2A1 is promising therapeutic DNA vaccine.…”

Section: Introductionmentioning

confidence: 99%

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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

et al. 2019

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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.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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“…A therapeutic DNA vaccine encoding chicken Type II collagen (CCII), termed pcDNA-CCOL2A1 was compared with methotrexate to evaluate their effects on cellular and humoral immune responses in normal rats [50]. In this study, vaccinating normal rats with pcDNA-CCOL2A1 did not result in the production of anti-CCII antibodies.…”

Section: Type II Collagen Vaccinesmentioning

confidence: 92%

Vaccine development for rheumatoid arthritis

Malemud¹

2015

Glob Vaccines Immunol

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“…DNA vaccination delivers plasmid DNA encoding the antigen and triggers an immune response [118,119]. DNA vaccination of CD40 targeting dendritic cells was reported to be protective of Heymann nephritis (HN) in an experimental rat model of autoimmune-mediated membranous nephritis [120].…”

Section: Targeting Cd40 Contributes To Therapeutic Treatments Of Kidnmentioning

confidence: 99%

CD40/CD40L Signaling as a Promising Therapeutic Target for the Treatment of Renal Disease

Zhang

Breidenbach

Russell

et al. 2020

JCM

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The cluster of differentiation 40 (CD40) is activated by the CD40 ligand (CD40L) in a variety of diverse cells types and regulates important processes associated with kidney disease. The CD40/CD40L signaling cascade has been comprehensively studied for its roles in immune functions, whereas the signaling axis involved in local kidney injury has only drawn attention in recent years. Clinical studies have revealed that circulating levels of soluble CD40L (sCD40L) are associated with renal function in the setting of kidney disease. Levels of the circulating CD40 receptor (sCD40), sCD40L, and local CD40 expression are tightly related to renal injury in different types of kidney disease. Additionally, various kidney cell types have been identified as non-professional antigen-presenting cells (APCs) that express CD40 on the cell membrane, which contributes to the interactions between immune cells and local kidney cells during the development of kidney injury. Although the potential for adverse CD40 signaling in kidney cells has been reported in several studies, a summary of those studies focusing on the role of CD40 signaling in the development of kidney disease is lacking. In this review, we describe the outcomes of recent studies and summarize the potential therapeutic methods for kidney disease which target CD40.

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Evaluation of humoral and cellular immune responses to a DNA vaccine encoding chicken type II collagen for rheumatoid arthritis in normal rats

Cited by 11 publications

References 28 publications

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

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

Vaccine development for rheumatoid arthritis

CD40/CD40L Signaling as a Promising Therapeutic Target for the Treatment of Renal Disease

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