Virus-like particles and capsomeres are potent vaccines against cutaneous alpha HPVs

被引:22
作者
Senger, Tilo [1 ]
Schaedlich, Lysann [1 ]
Textor, Sonja [1 ]
Klein, Corinna [1 ]
Michael, Kristina M. [1 ]
Buck, Christopher B. [2 ]
Gissmann, Lutz [1 ]
机构
[1] German Canc Res Ctr, Dept Genome Modificat & Carcinogenesis, D-69120 Heidelberg, Germany
[2] NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA
关键词
Papillomavirus; Cutaneous; Virus-like particle; Capsomeres; Immunogenicity; Prophylactic vaccine; HUMAN-PAPILLOMAVIRUS TYPE-16; MAJOR CAPSID PROTEIN; NEUTRALIZING ANTIBODIES; MONOCLONAL-ANTIBODIES; SUSTAINED EFFICACY; L1; CAPSOMERES; YOUNG-WOMEN; EXPRESSION; INFECTION; INDUCE;
D O I
10.1016/j.vaccine.2009.11.048
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The potential as prophylactic vaccines of L1-based particles from cutaneous genus alpha human papillomavirus (HPV) types has not been assessed so far. However, there is a high medical need for such vaccines since HPV-induced skin warts represent a major burden for children and for immunocompromised adults, such as organ transplant recipients. In this study, we have examined the immunogenicity of capsomeres and virus-like particles (VLPs) from HPV types 2, 27, and 57, the most frequent causative agents of skin warts. Immunization of mice induced immune responses resembling those observed upon vaccination with HPV 16 L1-based antigens. The antibody responses were cross-reactive but type-restricted in their neutralizing capacities. Application of adjuvant led to an enhanced potential to neutralize the respective immunogen type but did not improve cross-neutralization. Vaccination with capsomeres and VLPs from all four analyzed HPV types induced robust IFN gamma-associated T-cell activation. Immunization with mixed VLPs from HPV types 2, 27, and 57 triggered an antibody response similar to that after single-type immunization and capable of efficiently neutralizing all three types. Our results imply that vaccination with combinations of VLPs from cutaneous HPV types constitutes a promising strategy to prevent HPV-induced skin lesions. (C) 2009 Elsevier Ltd. All rights reserved.
引用
收藏
页码:1583 / 1593
页数:11
相关论文
共 65 条
[1]   Baculovirus expression system for heterologous multiprotein complexes [J].
Berger, I ;
Fitzgerald, DJ ;
Richmond, TJ .
NATURE BIOTECHNOLOGY, 2004, 22 (12) :1583-1587
[2]   The Impact of Quadrivalent Human Papillomavirus (HPV; Types 6, 11, 16, and 18) L1 Virus-Like Particle Vaccine on Infection and Disease Due to Oncogenic Nonvaccine HPV Types in Generally HPV-Naive Women Aged 16-26 Years [J].
Brown, Darron R. ;
Kjaer, Susanne K. ;
Sigurdsson, Kristjan ;
Iversen, Ole-Erik ;
Hernandez-Avila, Mauricio ;
Wheeler, Cosette M. ;
Perez, Gonzalo ;
Koutsky, Laura A. ;
Tay, Eng Hseon ;
Garcia, Patricia ;
Ault, Kevin A. ;
Garland, Suzanne M. ;
Leodolter, Sepp ;
Olsson, Sven-Eric ;
Tang, Grace W. K. ;
Ferris, Daron G. ;
Paavonen, Jorma ;
Steben, Marc ;
Bosch, F. Xavier ;
Dillner, Joakim ;
Joura, Elmar A. ;
Kurman, Robert J. ;
Majewski, Slawomir ;
Munoz, Nubia ;
Myers, Evan R. ;
Villa, Luisa L. ;
Taddeo, Frank J. ;
Roberts, Christine ;
Tadesse, Amha ;
Bryan, Janine ;
Lupinacci, Lisa C. ;
Giacoletti, Katherine E. D. ;
Sings, Heather L. ;
James, Margaret ;
Hesley, Teresa M. ;
Barra, Eliav .
JOURNAL OF INFECTIOUS DISEASES, 2009, 199 (07) :926-935
[3]   Efficient intracellular assembly of papillomaviral vectors [J].
Buck, CB ;
Pastrana, DV ;
Lowy, DR ;
Schiller, JT .
JOURNAL OF VIROLOGY, 2004, 78 (02) :751-757
[4]   Carrageenan is a potent inhibitor of papillomavirus infection [J].
Buck, Christopher B. ;
Thompson, Cynthia D. ;
Roberts, Jeffrey N. ;
Mueller, Martin ;
Lowy, Douglas R. ;
Schiller, John T. .
PLOS PATHOGENS, 2006, 2 (07) :671-680
[5]   Identification of a human papillomavirus type 16-specific epitope on the C-terminal arm of the major capsid protein L1 [J].
Carter, JJ ;
Wipf, GC ;
Benki, SF ;
Christensen, ND ;
Galloway, DA .
JOURNAL OF VIROLOGY, 2003, 77 (21) :11625-11632
[6]   Phylogenetic analysis of the human papillomavirus type 2 (HPV-2), HPV-27, and HPV-57 group, which is associated with common warts [J].
Chan, SY ;
Chew, SH ;
Egawa, K ;
Grussendorf-Conen, EI ;
Honda, Y ;
Rübben, A ;
Tan, KC ;
Bernard, HU .
VIROLOGY, 1997, 239 (02) :296-302
[7]   Papillomavirus capsid protein expression in Escherichia coli:: Purification and assembly of HPV11 and HPV16 L1 [J].
Chen, XJS ;
Casini, G ;
Harrison, SC ;
Garcea, RL .
JOURNAL OF MOLECULAR BIOLOGY, 2001, 307 (01) :173-182
[8]   Hybrid papillomavirus L1 molecules assemble into virus-like particles that reconstitute conformational epitopes and induce neutralizing antibodies to distinct HPV types [J].
Christensen, ND ;
Cladel, NM ;
Reed, CA ;
Budgeon, LR ;
Embers, ME ;
Skulsky, DM ;
McClements, WL ;
Ludmerer, SW ;
Jansen, KU .
VIROLOGY, 2001, 291 (02) :324-334
[9]   ASSEMBLED BACULOVIRUS-EXPRESSED HUMAN PAPILLOMAVIRUS TYPE-11 L1 CAPSID PROTEIN VIRUS-LIKE PARTICLES ARE RECOGNIZED BY NEUTRALIZING MONOCLONAL-ANTIBODIES AND INDUCE HIGH TITERS OF NEUTRALIZING ANTIBODIES [J].
CHRISTENSEN, ND ;
HOPFL, R ;
DIANGELO, SL ;
CLADEL, NM ;
PATRICK, SD ;
WELSH, PA ;
BUDGEON, LR ;
REED, CA ;
KREIDER, JW .
JOURNAL OF GENERAL VIROLOGY, 1994, 75 :2271-2276
[10]   Identification of two cross-neutralizing linear epitopes within the L1 major capsid protein of human papillomaviruses [J].
Combita, AL ;
Touzé, A ;
Bousarghin, L ;
Christensen, ND ;
Coursaget, P .
JOURNAL OF VIROLOGY, 2002, 76 (13) :6480-6486