嵌合布鲁菌BCSP31病毒样颗粒的免疫效果评价
|
摘要
新城疫病毒样颗粒已开发成一种高效递送外源蛋白的载体平台。本研究在小鼠模型中开展了嵌合布鲁菌BCSP31病毒样颗粒(BCSP31-cVLPs)免疫原性及其保护效力评价。体内试验数据表明,BCSP31-cVLPs能有效激活脾脏中树突状细胞,进而促进初始型CD3~+CD4~+ T的活化。ELISA法检测小鼠血清结果表明,BCSP31-cVLPs可刺激机体产生针对重组BCSP31蛋白的特异性抗体水平,且呈剂量依赖性。流式细胞术检测结果显示,BCSP31-cVLPs可激活T细胞并使其分化。攻毒结果表明,BCSP31-cVLPs具有与疫苗株M5相当的免疫保护效力。本研究为新型布鲁菌疫苗的研制提供了数据支撑,并扩展了新城疫病毒样颗粒疫苗载体平台的应用。
Newcastle disease virus-like particles have been developed as a vector platform for efficient delivery of foreign proteins.In this study,the immunogenicity and protective efficacy of chimeric Brucella BCSP31 virus-like particles(BCSP31-cVLPs) were evaluated in a mouse model.In vivo data indicate that BCSP31-cVLPs can effectively activate dendritic cells in the spleen and further promote the activation of the original CD3~+CD4~+ T.ELISA results showed that BCSP31-cVLPs stimulated the body to produce specific antibody against recombinant BCSP31 protein in a dose-dependent manner.Flow cytometry results showed that BCSP31-cVLPs can effectively activate T lymphocytes and induce differentiation.The results of the challenge showed that BCSP31-cVLPs have comparable immunoprotective efficacy to vaccine strain M5.In summary,this study provides data support for the development of a new Brucella vaccine and extends the application of the Newcastle disease virus-like particle vaccine vector platform.
Newcastle disease virus-like particles have been developed as a vector platform for efficient delivery of foreign proteins.In this study,the immunogenicity and protective efficacy of chimeric Brucella BCSP31 virus-like particles(BCSP31-cVLPs) were evaluated in a mouse model.In vivo data indicate that BCSP31-cVLPs can effectively activate dendritic cells in the spleen and further promote the activation of the original CD3~+CD4~+ T.ELISA results showed that BCSP31-cVLPs stimulated the body to produce specific antibody against recombinant BCSP31 protein in a dose-dependent manner.Flow cytometry results showed that BCSP31-cVLPs can effectively activate T lymphocytes and induce differentiation.The results of the challenge showed that BCSP31-cVLPs have comparable immunoprotective efficacy to vaccine strain M5.In summary,this study provides data support for the development of a new Brucella vaccine and extends the application of the Newcastle disease virus-like particle vaccine vector platform.
引文
[1] 袁乾亮,丁佳欣,高一丹,等.基因Ⅶ 型新城疫病毒样颗粒作为疫苗候选株的免疫效果[J].中国兽医学报,2017,37(2):201-205.
[2] PANTUA H D,MCGINNES L W,PEEPLES M E,et al.Requirements for the assembly and release of Newcastle disease virus-like particles[J].J Virol,2006,80(22):11062-11073.
[3] OGEMBO J G,MURASWKI M R,MCGINNES L W,et al.A chimeric EBV gp350/220-based VLP replicates the virion B-cell attachment mechanism and elicits long-lasting neutralizing antibodies in mice[J].J Transl Med,2015,13(1):50.
[4] 丁佳欣,钱晶,徐小洪,等.新城疫病毒样颗粒对树突状细胞成熟的影响[J].中国兽医学报,2017,37(8):1485-1489.
[5] QIAN J,XU X,DING J,et al.Newcastle disease virus-like particles induce DC maturation through TLR4/NF-?°B pathway and facilitate DC migration by CCR7-CCL19/CCL21 axis[J].Vet Microbiol,2017,203:158-166.
[6] 金宁一,胡仲明,冯书章.新编人兽共患病学[M].北京:科学出版社,2007.
[7] 景志刚,严家瑞,范伟兴.布鲁菌病疫苗研究进展[J].中国人兽共患病学报,2016,32(2):188-199.
[8] 李鹏,罗德炎,高永辉,等.布氏杆菌BCSP31/pVAX1重组表达质粒的构建及其免疫保护效果的研究[J].中国人兽共患病学报,2006,22(6):493-497.
[9] KIM W K,MOON J Y,SUK K,et al.Comparison between immunization routes of live attenuated Salmonella typhimurium strains expressing BCSP31,Omp3b,and SOD of Brucella abortusin murine model[J].Front Microbiol,2016,7(346):550.
[10] 李金斗,钱晶,丁佳欣,等.GPI锚定蛋白介导嵌合新城疫病毒样颗粒的组装[J].中国兽医学报,2017,37(6):969-975.
[11] MCGINNES L W,GRAVEL K A,FINBERG R W,et al.Assembly and immunological properties of Newcastle disease virus-like particles containing the respiratory syncytial virus F and G proteins[J].J Virol,2011,85(1):366.
[12] MCGINNES L W,PANTUA H,LALIBERTE J P,et al.Assembly and biological and immunological properties of Newcastle disease virus-like particles[J].J Virol,2010,84(9):4513-4523.
[13] PATEL J M,KIM M C,VARTABEDIAN V F,et al.Protein transfer-mediated surface engineering to adjuvantate virus-like nanoparticles for enhanced anti-viral immune responses[J].Nanomedicine,2015,11(5):1097-1107.
[14] MONA M,ARIANE G,MONIQUE V,et al.Interaction of viral capsid-derived virus-like particles (VLPs) with the innate immune system[J].Vaccines(Basel),2018,6(3).E37.doi:10.3390/vaccines6030037.
[15] 董薇,蔡美英.树突状细胞与T细胞免疫反应结果研究进展[J].中国免疫学杂志,2005,21(2):155-158.
[16] KIM K H,LEE Y T,HWANG H S,et al.Virus-like particle vaccine containing the F protein of respiratory syncytial virus confers protection without pulmonary disease by modulating specific subsets of dendritic cells and effector T cells [J].J Virol,2015,89(22):11692.
[17] OLIVEIRA S C,GIAMBARTOLOMEI G H,CASSATARO J.Confronting the barriers to develop novel vaccines against brucellosis[J].Expert Rev Vaccines,2011,10(9):1291-1305.
[2] PANTUA H D,MCGINNES L W,PEEPLES M E,et al.Requirements for the assembly and release of Newcastle disease virus-like particles[J].J Virol,2006,80(22):11062-11073.
[3] OGEMBO J G,MURASWKI M R,MCGINNES L W,et al.A chimeric EBV gp350/220-based VLP replicates the virion B-cell attachment mechanism and elicits long-lasting neutralizing antibodies in mice[J].J Transl Med,2015,13(1):50.
[4] 丁佳欣,钱晶,徐小洪,等.新城疫病毒样颗粒对树突状细胞成熟的影响[J].中国兽医学报,2017,37(8):1485-1489.
[5] QIAN J,XU X,DING J,et al.Newcastle disease virus-like particles induce DC maturation through TLR4/NF-?°B pathway and facilitate DC migration by CCR7-CCL19/CCL21 axis[J].Vet Microbiol,2017,203:158-166.
[6] 金宁一,胡仲明,冯书章.新编人兽共患病学[M].北京:科学出版社,2007.
[7] 景志刚,严家瑞,范伟兴.布鲁菌病疫苗研究进展[J].中国人兽共患病学报,2016,32(2):188-199.
[8] 李鹏,罗德炎,高永辉,等.布氏杆菌BCSP31/pVAX1重组表达质粒的构建及其免疫保护效果的研究[J].中国人兽共患病学报,2006,22(6):493-497.
[9] KIM W K,MOON J Y,SUK K,et al.Comparison between immunization routes of live attenuated Salmonella typhimurium strains expressing BCSP31,Omp3b,and SOD of Brucella abortusin murine model[J].Front Microbiol,2016,7(346):550.
[10] 李金斗,钱晶,丁佳欣,等.GPI锚定蛋白介导嵌合新城疫病毒样颗粒的组装[J].中国兽医学报,2017,37(6):969-975.
[11] MCGINNES L W,GRAVEL K A,FINBERG R W,et al.Assembly and immunological properties of Newcastle disease virus-like particles containing the respiratory syncytial virus F and G proteins[J].J Virol,2011,85(1):366.
[12] MCGINNES L W,PANTUA H,LALIBERTE J P,et al.Assembly and biological and immunological properties of Newcastle disease virus-like particles[J].J Virol,2010,84(9):4513-4523.
[13] PATEL J M,KIM M C,VARTABEDIAN V F,et al.Protein transfer-mediated surface engineering to adjuvantate virus-like nanoparticles for enhanced anti-viral immune responses[J].Nanomedicine,2015,11(5):1097-1107.
[14] MONA M,ARIANE G,MONIQUE V,et al.Interaction of viral capsid-derived virus-like particles (VLPs) with the innate immune system[J].Vaccines(Basel),2018,6(3).E37.doi:10.3390/vaccines6030037.
[15] 董薇,蔡美英.树突状细胞与T细胞免疫反应结果研究进展[J].中国免疫学杂志,2005,21(2):155-158.
[16] KIM K H,LEE Y T,HWANG H S,et al.Virus-like particle vaccine containing the F protein of respiratory syncytial virus confers protection without pulmonary disease by modulating specific subsets of dendritic cells and effector T cells [J].J Virol,2015,89(22):11692.
[17] OLIVEIRA S C,GIAMBARTOLOMEI G H,CASSATARO J.Confronting the barriers to develop novel vaccines against brucellosis[J].Expert Rev Vaccines,2011,10(9):1291-1305.