Characterization and evaluation of the immune responses elicited by a novel human papillomavirus (HPV) therapeutic vaccine: HPV 16E7-HBcAg-Hsp65 fusion protein

被引:8
作者
Zhou, Chao-Ming [1 ]
Zhang, Gao-Xia [1 ]
Ma, Xin-Xing [1 ]
机构
[1] Shanghai Zerun Biotechnol Co Ltd, Dept Qual Res, Shanghai 201203, Peoples R China
关键词
Human papillomaviruses; Therapeutic vaccine; Cellular immune response; Humoral immune response; Immunogenicity; ANTITUMOR IMMUNITY; ELISPOT-ASSAY; MOUSE MODEL; T-CELLS; MEMORY; TUMOR; IMMUNOTHERAPY; INDUCTION; CANCER;
D O I
10.1016/j.jviromet.2013.10.033
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Human papillomaviruses (HPV), particularly HPV16, are associated with most cervical cancers. Currently, although prophylactic vaccines have been developed, there is still an urgent need to develop therapeutic HPV vaccines. In this study, a novel fusion protein, HPV 16 E7-HBcAg-Hsp65 (VR111), with the goal of increasing anti-HPV16 cellular immunity was developed. VR111 was analyzed using SDS-PAGE, western-blotting, capillary isoelectric focusing (cIEF), analytical ultracentrifugation (AUC) and dynamic light scattering (DLS). Gamma interferon (IFN-gamma) secretion assay was performed by enzyme-linked immunospot (ELISPOT) and ELISA to test their ability to induce cellular immune response. Significant correlation between ELISPOT and ELISA was observed (r = 0.8680, p < 0.0001). It was shown that VR111 could induce a significant increase in E7-specific CD8(+) T cell responses. Humoral immune response was also observed. The antibody titer levels were measured by ELISA. These results indicated that VR111 was a promising therapeutic vaccine for treatment of cervical cancer with possible therapeutic potential in clinical settings. (C) 2013 Elsevier B.V. All rights reserved.
引用
收藏
页码:1 / 6
页数:6
相关论文
共 32 条
[1]   Introducing HPV vaccine in developing countries - Key challenges and issues [J].
Agosti, Jan M. ;
Goldie, Sue J. .
NEW ENGLAND JOURNAL OF MEDICINE, 2007, 356 (19) :1908-1910
[2]   Accelerated CD8+ T-cell memory and prime-boost response after dendritic-cell vaccination [J].
Badovinac, VP ;
Messingham, KAN ;
Jabbari, A ;
Haring, JS ;
Harty, JT .
NATURE MEDICINE, 2005, 11 (07) :748-756
[3]   PREVALENCE OF HUMAN PAPILLOMAVIRUS IN CERVICAL-CANCER - A WORLDWIDE PERSPECTIVE [J].
BOSCH, FX ;
MANOS, MM ;
MUNOZ, N ;
SHERMAN, M ;
JANSEN, AM ;
PETO, J ;
SCHIFFMAN, MH ;
MORENO, V ;
KURMAN, R ;
SHAH, KV ;
ALIHONOU, E ;
BAYO, S ;
MOKHTAR, HC ;
CHICAREON, S ;
DAUDT, A ;
DELOSRIOS, E ;
GHADIRIAN, P ;
KITINYA, JN ;
KOULIBALY, M ;
NGELANGEL, C ;
TINTORE, LMP ;
RIOSDALENZ, JL ;
SARJADI ;
SCHNEIDER, A ;
TAFUR, L ;
TEYSSIE, AR ;
ROLON, PA ;
TORROELLA, M ;
TAPIA, AV ;
WABINGA, HR ;
ZATONSKI, W ;
SYLLA, B ;
VIZCAINO, P ;
MAGNIN, D ;
KALDOR, J ;
GREER, C ;
WHEELER, C .
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1995, 87 (11) :796-802
[4]   A proposed mechanism for the induction of cytotoxic T lymphocyte production by heat shock fusion proteins [J].
Cho, BK ;
Palliser, D ;
Guillen, E ;
Wisniewski, J ;
Young, RA ;
Chen, JZ ;
Eisen, HN .
IMMUNITY, 2000, 12 (03) :263-272
[5]   Immunotherapy of a human papillomavirus (HPV) type 16 E7-expressing tumour by administration of fusion protein comprising Mycobacterium bovis bacille Calmette-Guerin (BCG) hsp65 and HPV16 E7 [J].
Chu, NR ;
Wu, HB ;
Wu, TC ;
Boux, LJ ;
Siegel, MI ;
Mizzen, LA .
CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2000, 121 (02) :216-225
[6]   CD4+ T cell-mediated antigen-specific immunotherapy in a mouse model of cervical cancer [J].
Daniel, D ;
Chiu, C ;
Giraudo, E ;
Inoue, M ;
Mizzen, LA ;
Chu, NR ;
Hanahan, D .
CANCER RESEARCH, 2005, 65 (05) :2018-2025
[7]   Evidence for a causal association between human papillomavirus and a subset of head and neck cancers [J].
Gillison, ML ;
Koch, WM ;
Capone, RB ;
Spafford, M ;
Westra, WH ;
Wu, L ;
Zahurak, ML ;
Daniel, RW ;
Viglione, M ;
Symer, DE ;
Shah, KV ;
Sidransky, D .
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2000, 92 (09) :709-720
[8]  
*GLAXOSMITHKLINE, 2007, CERV PROD INS
[9]   A novel fusion protein-based vaccine comprising a cell penetrating and immunostimulatory peptide linked to human papillomavirus (HPV) type 16 E7 antigen generates potent immunologic and anti-tumor responses in mice [J].
Granadillo, Milaid ;
Vallespi, Maribel G. ;
Batte, Aileen ;
Mendoza, Osmany ;
Soria, Yordanka ;
Lugo, Victoria M. ;
Torrens, Isis .
VACCINE, 2011, 29 (05) :920-930
[10]  
Grunbaum Jo Anne, 2004, Morbidity and Mortality Weekly Report, V53, P1