This article was downloaded by: [University of Connecticut] On: 13 April 2015, At: 15:42 Publisher: Taylor & Francis Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Human Vaccines & Immunotherapeutics Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/khvi20
Evaluation of humoral and cellular immune responses to a DNA vaccine encoding chicken type II collagen for rheumatoid arthritis in normal rats a
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Zhao Xiao , Long Juan , Yun Song , Zhang Zhijiang , Jin Jing , Yu Kun , Hao Lina , Dai a
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a
a
a
a
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Dongfa , Ding Lili , Tan Liuxin , Liang Fei , Liu Nan , Yuan Fang , Sun Yuying & Xi Yongzhi
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Department of Immunology and National Center for Biomedicine Analysis, Beijing 307 Hospital Affiliated to Academy of Military Medical Sciences, No.8, Dongda Ave, Fengtai District, Beijing, 100071, P.R.China Accepted author version posted online: 12 Mar 2015.
Click for updates To cite this article: Zhao Xiao, Long Juan, Yun Song, Zhang Zhijiang, Jin Jing, Yu Kun, Hao Lina, Dai Dongfa, Ding Lili, Tan Liuxin, Liang Fei, Liu Nan, Yuan Fang, Sun Yuying & Xi Yongzhi (2015): Evaluation of humoral and cellular immune responses to a DNA vaccine encoding chicken type II collagen for rheumatoid arthritis in normal rats, Human Vaccines & Immunotherapeutics To link to this article: http://dx.doi.org/10.1080/21645515.2015.1010977
Disclaimer: This is a version of an unedited manuscript that has been accepted for publication. As a service to authors and researchers we are providing this version of the accepted manuscript (AM). Copyediting, typesetting, and review of the resulting proof will be undertaken on this manuscript before final publication of the Version of Record (VoR). During production and pre-press, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal relate to this version also.
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http:// www.tandfonline.com/page/terms-and-conditions
Research Article to Human Vaccine Immunther(revised 2014HV0637R-2) Evaluation of Humoral and Cellular Immune Responses to a DNA Vaccine Encoding Chicken Type II Collagen for Rheumatoid Arthritis in Normal Rats
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Zhao Xiao*, Long Juan*, Yun Song, Zhang Zhijiang, Jin Jing, Yu Kun, Hao Lina, Dai Dongfa, Ding Lili, Tan Liuxin, Liang Fei, Liu Nan, Yuan Fang, Sun Yuying, Xi
cr
us
Department of Immunology and National Center for Biomedicine Analysis, Beijing 307 Hospital Affiliated to Academy of Military Medical Sciences, No.8, Dongda Ave, Fengtai
an
District, Beijing, 100071, P.R.China
*The following authors contributed equally to this work.
M
**To whom correspondence should be addressed:
ed
Department of Immunology and National Center for Biomedicine Analysis, Beijing 307 Hospital Affiliated to Academy of Military Medical Sciences, No.8, Dongda Ave, Fengtai Beijing, 100071, P.R.China; Tel: 86-10-66947276; Fax: 86-10-66947276;
pt
District,
Email: Xi YZ([email protected])
ce
Running title: Humoral and Cellular Immune Responses to a pcDNA-CCOL2A1 Vaccine Keywords: chicken type II procollagen, therapeutic DNA vaccine, rheumatoid arthritis,
Ac
Downloaded by [University of Connecticut] at 15:42 13 April 2015
Yongzhi**
cellular immunity, humoral immunity
Abbreviations used in this article: CCOL2A1, chicken type II procollagen gene; CCII, chicken type II collagen; RA, rheumatoid arthritis; CIA, collagen induced arthritis; MTX, methotrexate; IL, interleukin; MCP-1, monocyte chemotactic protein 1; MIP-1α, macrophage inflammatory protein-1 alpha; RANTES, regulated on activation in normal T-cell expressed
1
and secreted; RANKL, receptor activator for nuclear factor-κB ligand; G-CSF, granulocyte colony-stimulating factor; EAE, experimental autoimmune encephalomyelitis; NOD, spontaneous nonobese diabetic; MS, multiple sclerosis; DMARD, disease modifying
ip t
antirheumatic drug. Abstract
cr
us
finding a method for the specific inhibition of the inflammatory disease processes without the induction of generalized immunosuppression. Of note, the development of therapeutic DNA
an
vaccines and boosters that may restore immunological tolerance remains a high priority. pcDNA-CCOL2A1 is a therapeutic DNA vaccine encoding chicken type II collagen(CCII)
M
this vaccine was developed by our laboratory and has been shown to exhibit efficacy
ed
comparable to that of the current “gold standard” treatment, methotrexate (MTX). Here, we used enzyme-linked immunosorbent assays with anti-CII IgG antibodies, quantified the
pt
expression levels of Th1, Th2, and Th3 cytokines, and performed flow cytometric analyses of different T-cell subsets, including Th1, Th2, Th17, Tc, Ts, Treg, and CD4+CD29+T cells to
ce
systemically evaluate humoral and cellular immune responses to pcDNA-CCOL2A1 vaccine in normal rats. Similar to our observations at maximum dosage of 3mg/kg, vaccination of
Ac
Downloaded by [University of Connecticut] at 15:42 13 April 2015
A major challenge in the development of effective therapies for rheumatoid arthritis (RA) is
normal rats with 300μg/kg pcDNA-CCOL2A1 vaccine did not induce the production of anti-CII IgG. Furthermore, no significant changes were observed in the expression levels of pro-inflammatory cytokines interleukin (IL)-1α, IL-5, IL-6, IL-12(IL-23p40), monocyte chemotactic protein (MCP)-1, macrophage inflammatory protein (MIP)-1α, regulated on activation in normal T-cell expressed and secreted (RANTES), receptor activator for nuclear
2
factor-κB ligand (RANKL), and granulocyte colony-stimulating factor (G-CSF) or anti-inflammatory cytokines IL-4 and IL-10 in vaccinated normal rats relative to that in controls(P>0.05). However, transforming growth factor (TGF)-β levels were significantly
ip t
increased on days 10 and 14, while interferon (IFN)-γ and tumor necrosis factor (TNF)-α levels were significantly decreased on days 28 and 35 after vaccination(P0.05), with the exception of Treg cells, which were significantly reduced on days 14 and 21 after vaccination (P
Human Vaccines & Immunotherapeutics Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/khvi20
Evaluation of humoral and cellular immune responses to a DNA vaccine encoding chicken type II collagen for rheumatoid arthritis in normal rats a
a
a
a
a
a
a
Zhao Xiao , Long Juan , Yun Song , Zhang Zhijiang , Jin Jing , Yu Kun , Hao Lina , Dai a
a
a
a
a
a
a
Dongfa , Ding Lili , Tan Liuxin , Liang Fei , Liu Nan , Yuan Fang , Sun Yuying & Xi Yongzhi
a
a
Department of Immunology and National Center for Biomedicine Analysis, Beijing 307 Hospital Affiliated to Academy of Military Medical Sciences, No.8, Dongda Ave, Fengtai District, Beijing, 100071, P.R.China Accepted author version posted online: 12 Mar 2015.
Click for updates To cite this article: Zhao Xiao, Long Juan, Yun Song, Zhang Zhijiang, Jin Jing, Yu Kun, Hao Lina, Dai Dongfa, Ding Lili, Tan Liuxin, Liang Fei, Liu Nan, Yuan Fang, Sun Yuying & Xi Yongzhi (2015): Evaluation of humoral and cellular immune responses to a DNA vaccine encoding chicken type II collagen for rheumatoid arthritis in normal rats, Human Vaccines & Immunotherapeutics To link to this article: http://dx.doi.org/10.1080/21645515.2015.1010977
Disclaimer: This is a version of an unedited manuscript that has been accepted for publication. As a service to authors and researchers we are providing this version of the accepted manuscript (AM). Copyediting, typesetting, and review of the resulting proof will be undertaken on this manuscript before final publication of the Version of Record (VoR). During production and pre-press, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal relate to this version also.
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http:// www.tandfonline.com/page/terms-and-conditions
Research Article to Human Vaccine Immunther(revised 2014HV0637R-2) Evaluation of Humoral and Cellular Immune Responses to a DNA Vaccine Encoding Chicken Type II Collagen for Rheumatoid Arthritis in Normal Rats
ip t
Zhao Xiao*, Long Juan*, Yun Song, Zhang Zhijiang, Jin Jing, Yu Kun, Hao Lina, Dai Dongfa, Ding Lili, Tan Liuxin, Liang Fei, Liu Nan, Yuan Fang, Sun Yuying, Xi
cr
us
Department of Immunology and National Center for Biomedicine Analysis, Beijing 307 Hospital Affiliated to Academy of Military Medical Sciences, No.8, Dongda Ave, Fengtai
an
District, Beijing, 100071, P.R.China
*The following authors contributed equally to this work.
M
**To whom correspondence should be addressed:
ed
Department of Immunology and National Center for Biomedicine Analysis, Beijing 307 Hospital Affiliated to Academy of Military Medical Sciences, No.8, Dongda Ave, Fengtai Beijing, 100071, P.R.China; Tel: 86-10-66947276; Fax: 86-10-66947276;
pt
District,
Email: Xi YZ([email protected])
ce
Running title: Humoral and Cellular Immune Responses to a pcDNA-CCOL2A1 Vaccine Keywords: chicken type II procollagen, therapeutic DNA vaccine, rheumatoid arthritis,
Ac
Downloaded by [University of Connecticut] at 15:42 13 April 2015
Yongzhi**
cellular immunity, humoral immunity
Abbreviations used in this article: CCOL2A1, chicken type II procollagen gene; CCII, chicken type II collagen; RA, rheumatoid arthritis; CIA, collagen induced arthritis; MTX, methotrexate; IL, interleukin; MCP-1, monocyte chemotactic protein 1; MIP-1α, macrophage inflammatory protein-1 alpha; RANTES, regulated on activation in normal T-cell expressed
1
and secreted; RANKL, receptor activator for nuclear factor-κB ligand; G-CSF, granulocyte colony-stimulating factor; EAE, experimental autoimmune encephalomyelitis; NOD, spontaneous nonobese diabetic; MS, multiple sclerosis; DMARD, disease modifying
ip t
antirheumatic drug. Abstract
cr
us
finding a method for the specific inhibition of the inflammatory disease processes without the induction of generalized immunosuppression. Of note, the development of therapeutic DNA
an
vaccines and boosters that may restore immunological tolerance remains a high priority. pcDNA-CCOL2A1 is a therapeutic DNA vaccine encoding chicken type II collagen(CCII)
M
this vaccine was developed by our laboratory and has been shown to exhibit efficacy
ed
comparable to that of the current “gold standard” treatment, methotrexate (MTX). Here, we used enzyme-linked immunosorbent assays with anti-CII IgG antibodies, quantified the
pt
expression levels of Th1, Th2, and Th3 cytokines, and performed flow cytometric analyses of different T-cell subsets, including Th1, Th2, Th17, Tc, Ts, Treg, and CD4+CD29+T cells to
ce
systemically evaluate humoral and cellular immune responses to pcDNA-CCOL2A1 vaccine in normal rats. Similar to our observations at maximum dosage of 3mg/kg, vaccination of
Ac
Downloaded by [University of Connecticut] at 15:42 13 April 2015
A major challenge in the development of effective therapies for rheumatoid arthritis (RA) is
normal rats with 300μg/kg pcDNA-CCOL2A1 vaccine did not induce the production of anti-CII IgG. Furthermore, no significant changes were observed in the expression levels of pro-inflammatory cytokines interleukin (IL)-1α, IL-5, IL-6, IL-12(IL-23p40), monocyte chemotactic protein (MCP)-1, macrophage inflammatory protein (MIP)-1α, regulated on activation in normal T-cell expressed and secreted (RANTES), receptor activator for nuclear
2
factor-κB ligand (RANKL), and granulocyte colony-stimulating factor (G-CSF) or anti-inflammatory cytokines IL-4 and IL-10 in vaccinated normal rats relative to that in controls(P>0.05). However, transforming growth factor (TGF)-β levels were significantly
ip t
increased on days 10 and 14, while interferon (IFN)-γ and tumor necrosis factor (TNF)-α levels were significantly decreased on days 28 and 35 after vaccination(P0.05), with the exception of Treg cells, which were significantly reduced on days 14 and 21 after vaccination (P
