Human papillomavirus type 16 L1E7 chimeric capsomeres have prophylactic and therapeutic efficacy against papillomavirus in mice

被引:24
作者
Bian, Tao [1 ,2 ]
Wang, Yue [1 ]
Lu, Zhenhua [2 ]
Ye, Zhenmei [2 ]
Zhao, Li [2 ]
Ren, Jiao [2 ]
Zhang, Hui [2 ]
Ruan, Li [2 ]
Tian, Houwen [2 ]
机构
[1] Chinese Ctr Dis Control & Prevent, Natl Inst Viral Dis Control & Prevent, Div Hepatitis, Beijing 100052, Peoples R China
[2] Chinese Ctr Dis Control & Prevent, Natl Inst Viral Dis Control & Prevent, Biotech Ctr Viral Dis Emergency, Beijing 100052, Peoples R China
关键词
D O I
10.1158/1535-7163.MCT-07-2015
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Genital human papillomavirus (HPV) infection is the primary cause of cervical cancer in women. Although the HPV recombinant L1 protein was recently licensed as an available vaccine, it has numerous shortcomings. New vaccination strategies should be considered. To enable the design of a prophylactic and therapeutic low-cost vaccine candidate, chimeric HPV16 L1(Delta C34)E7(N1-60) capsomeres were produced in Escherichia coli. The immune characteristics and potential prophylactic and therapeutic effects of these capsomeres were examined in C5713L/6 mice. Following protein purification and renaturation, the majority of the recombinant chimeric proteins (L1(Delta C34)E7(N1-60)) assembled into capsomeres. These capsomeres were able to induce conformational and neutralizing antibodies against HPV virus-like particles and trigger cell-mediated specific immune responses against the L1 and E7 pepticles. In vivo tumor challenge assays showed that mice immunized with the capsomeres were protected against a challenge with both C3 and TC-1 tumor cells. Furthermore, in vivo tumor rejection assays showed that capsomeres have therapeutic efficacy in mice following inoculation with C3 and TC-1 tumor cells. Chimeric capsomeres are capable of preventing and eliminating HPV16 infection. Therefore, our study has provided an economical vaccine candidate.
引用
收藏
页码:1329 / 1335
页数:7
相关论文
共 36 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]   The causal relation between human papillomavirus and cervical cancer [J].
Bosch, FX ;
Lorincz, A ;
Muñoz, N ;
Meijer, CJLM ;
Shah, KV .
JOURNAL OF CLINICAL PATHOLOGY, 2002, 55 (04) :244-265
[3]   Construction and characterisation of a recombinant vaccinia was expressing human papillomavirus proteins for immunotherapy of cervical cancer [J].
Boursnell, MEG ;
Rutherford, E ;
Hickling, JK ;
Rollinson, EA ;
Munro, AJ ;
Rolley, N ;
McLean, CS ;
Borysiewicz, LK ;
Vousden, K ;
Inglis, SC .
VACCINE, 1996, 14 (16) :1485-1494
[4]   Therapeutic vaccination for HPV induced cervical cancers [J].
Brinkman, Joeli A. ;
Hughes, Sarah H. ;
Stone, Pamela ;
Caffrey, Angela S. ;
Muderspach, Laila I. ;
Roman, Lynda D. ;
Weber, Jeffrey S. ;
Kast, W. Martin .
DISEASE MARKERS, 2007, 23 (04) :337-351
[5]   Impact of the human papilloma vaccine on cervical cancer [J].
Chan, John K. ;
Berek, Jonathan S. .
JOURNAL OF CLINICAL ONCOLOGY, 2007, 25 (20) :2975-2982
[6]   HUMAN PAPILLOMAVIRUS TYPE-16 NUCLEOPROTEIN-E7 IS A TUMOR REJECTION ANTIGEN [J].
CHEN, LP ;
THOMAS, EK ;
HU, SL ;
HELLSTROM, I ;
HELLSTROM, KE .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (01) :110-114
[7]   Structure of small virus-like particles assembled from the L1 protein of human papillomavirus 16 [J].
Chen, XJS ;
Garcea, RL ;
Goldberg, I ;
Casini, G ;
Harrison, SC .
MOLECULAR CELL, 2000, 5 (03) :557-567
[8]   Heterologous boosting increases immunogenicity of chimeric papillomavirus virus-like particle vaccines [J].
Da Silva, DA ;
Schiller, JT ;
Kast, WM .
VACCINE, 2003, 21 (23) :3219-3227
[9]   Human papillomaviruses: General features [J].
Favre, M ;
Ramoz, N ;
Orth, G .
CLINICS IN DERMATOLOGY, 1997, 15 (02) :181-198
[10]   VACCINATION WITH CYTOTOXIC T-LYMPHOCYTE EPITOPE-CONTAINING PEPTIDE PROTECTS AGAINST A TUMOR-INDUCED BY HUMAN PAPILLOMAVIRUS TYPE-16-TRANSFORMED CELLS [J].
FELTKAMP, MCW ;
SMITS, HL ;
VIERBOOM, MPM ;
MINNAAR, RP ;
DEJONGH, BM ;
DRIJFHOUT, JW ;
TERSCHEGGET, J ;
MELIEF, CJM ;
KAST, WM .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1993, 23 (09) :2242-2249