Generation of chimeric HBc proteins with epitopes in E.coli: Formation of virus-like particles and a potent inducer of antigen-specific cytotoxic immune response and anti-tumor effect in vivo
作者： Yan Zhang , Shuxia Song , Chunyan Liu , Yue Wang , Xian Xian
DOI: 10.1016/J.CELLIMM.2007.07.003
关键词: HBcAg 、 Cytotoxic T cell 、 Fusion protein 、 Virology 、 CTL* 、 Antigen 、 Biology 、 Immunogen 、 CD8 、 Molecular biology 、 Epitope 、 Immunology
摘要: The major aim of the project was to develop virus-like particles (VLPs) displaying single or multi-epitope hepatocellular carcinomas (HCC) in Escherichia coli and evaluate effect on inducing Ag-specific CD8(+) T cell response antitumor efficacy as candidate vaccines. To this end, hepatitis B virus core (HBc) were used a carrier HCC epitopes. Four epitopes MAGE-1(278-286aa), MAGE-3(271-279aa), AFP1 (158-166aa) AFP2 (542-550aa) fused 3' terminus truncated HBV gene, respectively, conjunctively. Not all recombinant plasmids led expression chimeric proteins strain E. BL21 (DE3), but which are expressed inclusion bodies resulted formation complete "mature" VLPs. coli-derived HBc(1-144) protein self-assembled into VLPs that both morphologically physically similar wild-type ones they still remained activity after purification refolding from 6M urea solution. We also showed could be internalized presented by DCs vitro. Additionally, pulsed with HBc-VLPs induce stronger CTL greater IFN-gamma secretion responding cells compared peptid-pulsed DCs. In B16-pIR-HH tumor therapy model, growth established tumors significantly inhibited immunization using VLP-pulsed DCs, resulting higher survival rate immunized animals. Thus, results current study have demonstrated principal possibility VLP basis HBcAg for creation new type HCC-specific immunogen.
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sci-hub.se 参考文章(32)
Arik Cooper, Guy Tal, Ofer Lider, Yosef Shaul, Cytokine Induction by the Hepatitis B Virus Capsid in Macrophages Is Facilitated by Membrane Heparan Sulfate and Involves TLR2 The Journal of Immunology. ,vol. 175, pp. 3165- 3176 ,(2005) , 10.4049/JIMMUNOL.175.5.3165
Petra Lenz, Patricia M. Day, Yuk-Ying S. Pang, Stephan A. Frye, Peter N. Jensen, Douglas R. Lowy, John T. Schiller, Papillomavirus-Like Particles Induce Acute Activation of Dendritic Cells Journal of Immunology. ,vol. 166, pp. 5346- 5355 ,(2001) , 10.4049/JIMMUNOL.166.9.5346
P. Pumpens, G.P. Borisova, R.A. Crowther, E. Grens, HEPATITIS B VIRUS CORE PARTICLES AS EPITOPE CARRIERS Intervirology. ,vol. 38, pp. 63- 74 ,(1995) , 10.1159/000150415
K Melber, R Schirmbeck, J Reimann, Z A Janowicz, A Kuhröber, Immunization with soluble hepatitis B virus surface protein elicits murine H-2 class I-restricted CD8+ cytotoxic T lymphocyte responses in vivo. Journal of Immunology. ,vol. 152, pp. 1110- 1119 ,(1994)
Walter> Fiers, Sabine Neirynck, Tom Deroo, Xavier Saelens, Willy Min Jou, Soluble recombinant influenza vaccines. Philosophical Transactions of the Royal Society B. ,vol. 356, pp. 1961- 1963 ,(2001) , 10.1098/RSTB.2001.0980
A Miyanohara, T Imamura, M Araki, K Sugawara, N Ohtomo, K Matsubara, Expression of hepatitis B virus core antigen gene in Saccharomyces cerevisiae: synthesis of two polypeptides translated from different initiation codons. Journal of Virology. ,vol. 59, pp. 176- 180 ,(1986) , 10.1128/JVI.59.1.176-180.1986
B. E. Clarke, S. E. Newton, A. R. Carroll, M. J. Francis, G. Appleyard, A. D. Syred, P. E. Highfield, D. J. Rowlands, F. Brown, Improved immunogenicity of a peptide epitope after fusion to hepatitis B core protein. Nature. ,vol. 330, pp. 381- 384 ,(1987) , 10.1038/330381A0
Marina De Filette, Willy Min Jou, Ashley Birkett, Katie Lyons, Brian Schultz, Anne Tonkyro, Stephanie Resch, Walter Fiers, Universal influenza A vaccine: Optimization of M2-based constructs Virology. ,vol. 337, pp. 149- 161 ,(2005) , 10.1016/J.VIROL.2005.04.004
He Xiao-wen, Sun Shu-han, Hu Zhen-lin, Li Jun, Jiang Lei, Zhou Feng-juan, Zhang Ya-nan, Guo Ying-Jun, Augmented humoral and cellular immune responses of a hepatitis B DNA vaccine encoding HBsAg by protein boosting Vaccine. ,vol. 23, pp. 1649- 1656 ,(2005) , 10.1016/J.VACCINE.2004.10.013
W Fiers, M De Filette, A Birkett, S Neirynck, W Min Jou, A “universal” human influenza A vaccine Virus Research. ,vol. 103, pp. 173- 176 ,(2004) , 10.1016/J.VIRUSRES.2004.02.030