Therapeutic vaccination with papillomavirus E6 and E7 long peptides results in the control of both established virus-induced lesions and latently infected sites in a pre-clinical cottontail rabbit papillomavirus model

被引:88
作者
Vambutas, A
DeVoti, J
Nouri, M
Drijfhout, JW
Lipford, GB
Bonagura, VR
van der Burg, SH
Melief, CJM
机构
[1] Long Isl Jewish Med Ctr, N Shore Long Isl Jewish Res Inst, New Hyde Pk, NY 11040 USA
[2] Leiden Univ, Ctr Med, Dept Immunohematol, NL-2333 AA Leiden, Netherlands
[3] Blood Bank, NL-2333 AA Leiden, Netherlands
[4] Coley Pharmarceut, Wellesley, MA 02481 USA
关键词
peptides; recurrent respiratory papillomastosis; papillomavirus;
D O I
10.1016/j.vaccine.2005.04.049
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
This study was performed to test the therapeutic efficacy of overlapping long E6 and E7 peptides, containing both CD4+ T-helper and CD8+ CTL epitopes, on CRPV-induced lesions, which is an appropriate pre-clinical model for HPV diseases, including recurrent respiratory papillomatosis (RRP). Therapeutic peptide vaccination was able to significantly control wart growth (p < 0.01) and abrogate latent CRPV nfection (p=0.0006) compared to controls. Vaccination was associated with a T(H)1 T cell response, as suggested by a strong DTH skin test, antigen-specific proliferation of PBMC and a minimal IgG antibody response. Thus, this study shows promise for treatment of RRP by vaccination with long peptides. (c) 2005 Elsevier Ltd. All rights reserved.
引用
收藏
页码:5271 / 5280
页数:10
相关论文
共 50 条
[1]   Latent human papillomavirus infection is comparable in the larynx and trachea [J].
Abramson, AL ;
Nouri, M ;
Mullooly, V ;
Fisch, G ;
Steinberg, BM .
JOURNAL OF MEDICAL VIROLOGY, 2004, 72 (03) :473-477
[2]  
AMELLA CA, 1994, AM J PATHOL, V144, P1167
[3]  
Baines J, 2003, CLIN CANCER RES, V9, P2693
[4]   Divergent therapeutic and immunologic effects of oligodeoxynucleotides with distinct CpG motifs [J].
Ballas, ZK ;
Krieg, AM ;
Warren, T ;
Rasmussen, W ;
Davis, HL ;
Waldschmidt, M ;
Weiner, GJ .
JOURNAL OF IMMUNOLOGY, 2001, 167 (09) :4878-4886
[5]   HPV infections and immunosuppression [J].
Bavinck, JNB ;
Berkhout, RJM .
CLINICS IN DERMATOLOGY, 1997, 15 (03) :427-437
[6]   A review of human papillomavirus vaccines: From basic science to clinical trials [J].
Berry, JM ;
Palefsky, JM .
FRONTIERS IN BIOSCIENCE, 2003, 8 :S333-S345
[7]   Synthetic unmethylated cytosine-phosphate-guanosine oligodeoxynucleotides are potent stimulators of antileukemia responses in naive and bone marrow transplant recipients [J].
Blazar, BR ;
Krieg, AM ;
Taylor, PA .
BLOOD, 2001, 98 (04) :1217-1225
[8]   The rabbit viral skin papillomas and carcinomas: A model for the immunogenetics of HPV-associated carcinogenesis [J].
Breitburd, F ;
Salmon, J ;
Orth, G .
CLINICS IN DERMATOLOGY, 1997, 15 (02) :237-247
[9]   Enhanced dendritic cell maturation by TNF-α or cytidine-phosphate-guanosine DNA drives T cell activation in vitro and therapeutic anti-tumor immune responses in vivo [J].
Brunner, C ;
Seiderer, J ;
Schlamp, A ;
Bidlingmaier, M ;
Eigler, A ;
Haimerl, W ;
Lehr, HA ;
Krieg, AM ;
Hartmann, G ;
Endres, S .
JOURNAL OF IMMUNOLOGY, 2000, 165 (11) :6278-6286
[10]   Animal models of papillomavirus pathogenesis [J].
Campo, MS .
VIRUS RESEARCH, 2002, 89 (02) :249-261