title: Safety and immunogenicity of a novel therapeutic DNA vaccine encoding chicken type II collagen for rheumatoid arthritis in normal rats.
abstract: Current clinically available treatments for rheumatoid arthritis (RA) fail to cure the disease or unsatisfactorily halt disease progression. To overcome these limitations, the development of therapeutic DNA vaccines and boosters may offer new promising strategies. Because type II collagen (CII) as a critical autoantigen in RA and native chicken type II collagen (nCCII) has been used to effectively treat RA, we previously developed a novel therapeutic DNA vaccine encoding CCII (pcDNA-CCOL2A1) with efficacy comparable to that of the current "gold standard", methotrexate(MTX). Here, we systemically evaluated the safety and immunogenicity of the pcDNA-CCOL2A1 vaccine in normal Wistar rats. Group 1 received only a single intramuscular injection into the hind leg with pcDNA-CCOL2A1 at the maximum dosage of 3 mg/kg on day 0; Group 2 was injected with normal saline (NS) as a negative control. All rats were monitored daily for any systemic adverse events, reactions at the injection site, and changes in body weights. Plasma and tissues from all experimental rats were collected on day 14 for routine examinations of hematology and biochemistry parameters, anti-CII IgG antibody reactivity, and histopathology. Our results indicated clearly that at the maximum dosage of 3 mg/kg, the pcDNA-CCOL2A1 vaccine was safe and well-tolerated. No abnormal clinical signs or deaths occurred in the pcDNA-CCOL2A1 group compared with the NS group. Furthermore, no major alterations were observed in hematology, biochemistry, and histopathology, even at the maximum dose. In particularly, no anti-CII IgG antibodies were detected in vaccinated normal rats at 14 d after vaccination; this was relevant because we previously demonstrated that the pcDNA-CCOL2A1 vaccine, when administered at the therapeutic dosage of 300 μg/kg alone, did not induce anti-CII IgG antibody production and significantly reduced levels of anti-CII IgG antibodies in the plasma of rats with established collagen-induced arthritis (CIA). This is the first study demonstrating the safety and immunogenicity of a DNA vaccine encoding CCII for treating RA in normal rats. These results may support the use of this novel therapeutic DNA vaccine for the treatment of RA in the future.
authors.affiliation: a Department of Immunology and National Center for Biomedicine Analysis ; Beijing 307 Hospital Affiliated to Academy of Military Medical Sciences ; Beijing , PR China.
authors.forename: Long
authors.initials: L
authors.lastname: Juan
authors.affiliation: a Department of Immunology and National Center for Biomedicine Analysis ; Beijing 307 Hospital Affiliated to Academy of Military Medical Sciences ; Beijing , PR China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Xiao
authors.affiliation: a Department of Immunology and National Center for Biomedicine Analysis ; Beijing 307 Hospital Affiliated to Academy of Military Medical Sciences ; Beijing , PR China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Song
authors.affiliation: a Department of Immunology and National Center for Biomedicine Analysis ; Beijing 307 Hospital Affiliated to Academy of Military Medical Sciences ; Beijing , PR China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Zhijian
authors.affiliation: a Department of Immunology and National Center for Biomedicine Analysis ; Beijing 307 Hospital Affiliated to Academy of Military Medical Sciences ; Beijing , PR China.
authors.forename: Jin
authors.initials: J
authors.lastname: Jing
authors.affiliation: a Department of Immunology and National Center for Biomedicine Analysis ; Beijing 307 Hospital Affiliated to Academy of Military Medical Sciences ; Beijing , PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Kun
authors.affiliation: a Department of Immunology and National Center for Biomedicine Analysis ; Beijing 307 Hospital Affiliated to Academy of Military Medical Sciences ; Beijing , PR China.
authors.forename: Hao
authors.initials: H
authors.lastname: Yuna
authors.affiliation: a Department of Immunology and National Center for Biomedicine Analysis ; Beijing 307 Hospital Affiliated to Academy of Military Medical Sciences ; Beijing , PR China.
authors.forename: Dai
authors.initials: D
authors.lastname: Dongfa
authors.affiliation: a Department of Immunology and National Center for Biomedicine Analysis ; Beijing 307 Hospital Affiliated to Academy of Military Medical Sciences ; Beijing , PR China.
authors.forename: Ding
authors.initials: D
authors.lastname: Lili
authors.affiliation: a Department of Immunology and National Center for Biomedicine Analysis ; Beijing 307 Hospital Affiliated to Academy of Military Medical Sciences ; Beijing , PR China.
authors.forename: Tan
authors.initials: T
authors.lastname: Liuxin
authors.affiliation: a Department of Immunology and National Center for Biomedicine Analysis ; Beijing 307 Hospital Affiliated to Academy of Military Medical Sciences ; Beijing , PR China.
authors.forename: Liang
authors.initials: L
authors.lastname: Fei
authors.affiliation: a Department of Immunology and National Center for Biomedicine Analysis ; Beijing 307 Hospital Affiliated to Academy of Military Medical Sciences ; Beijing , PR China.
authors.forename: Liu
authors.initials: L
authors.lastname: Nan
authors.affiliation: a Department of Immunology and National Center for Biomedicine Analysis ; Beijing 307 Hospital Affiliated to Academy of Military Medical Sciences ; Beijing , PR China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Fang
authors.affiliation: a Department of Immunology and National Center for Biomedicine Analysis ; Beijing 307 Hospital Affiliated to Academy of Military Medical Sciences ; Beijing , PR China.
authors.forename: Sun
authors.initials: S
authors.lastname: Yuying
authors.affiliation: a Department of Immunology and National Center for Biomedicine Analysis ; Beijing 307 Hospital Affiliated to Academy of Military Medical Sciences ; Beijing , PR China.
authors.forename: Xi
authors.initials: X
authors.lastname: Yongzhi
mesh_terms: D000818:Animals; D000906:Antibodies / Q000097:blood; D000917:Antibody Formation / Q000276:immunology; D001169:Arthritis, Experimental / Q000628:therapy*; D001172:Arthritis, Rheumatoid / Q000628:therapy*; D001324:Autoantigens / Q000235:genetics / Q000276:immunology*; D002645:Chickens; D024043:Collagen Type II / Q000235:genetics / Q000276:immunology*; D005260:Female; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D019444:Vaccines, DNA / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*
chemical_list: D000906:Antibodies; D001324:Autoantigens; C511513:COL2A1 protein, rat; D024043:Collagen Type II; D019444:Vaccines, DNA
keywords: chicken type II procollagen; immunogenicity; rheumatoid arthritis; safety; therapeutic DNA vaccine