A virosomal immunization strategy against cervical cancer and pre-malignant cervical disease.
In this study, we demonstrate that fusion-active virosomes, containing recombinant human papillomavirus type 16 (HPV16) E7 protein antigen, are capable of inducing a robust class I MHC-restricted cytotoxic T-lymphocyte (CTL) response against HPV-transformed tumour cells in a murine model system. Virosomes are reconstituted viral envelopes, which do not contain the genetic material of the native virus. During the reconstitution process, protein antigens can be encapsulated within the virosomes. In the present study, we used virosomes derived from influenza virus. These virosomes retain the cell binding and membrane fusion characteristics of native influenza virus, and have the capacity to deliver encapsulated antigens to the cytosol of antigen-presenting cells through fusion from within acidic endosomes. After immunization of mice with virosomes containing encapsulated HPV16 E7 protein, the animals developed a strong E7-specific CTL response as assessed by 51Cr release measurements and MHC tetramer staining of spleen cells. Immunization with E7-containing virosomes also resulted in E7-specific antibody responses. In tumour challenge experiments, immunization of mice with E7-containing virosomes prevented tumour outgrowth in >70% of the animals. Thus, influenza-derived virosomes with encapsulated HPV E7 protein antigen act as an excellent vaccine delivery system for induction of cellular immunity against HPV-transformed cells and represent a promising immunotherapeutic vaccine for the treatment of (precursor lesions of) cervical cancer.
Bungener
Laura
L
Department of Medical Microbiology, Molecular Virology Section, University Medical Center Groningen, University of Groningen, the Netherlands.
de Mare
Arjan
A
de Vries-Idema
Jacqueline
J
Sehr
Peter
P
van der Zee
Ate
A
Wilschut
Jan
J
Daemen
Toos
T
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology; D002461:Cell Line, Transformed / Q000637:transplantation; D045744:Cell Line, Tumor; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D052162:Human papillomavirus 16 / Q000276:immunology; D006801:Humans; D007114:Immunization; D051379:Mice; D008810:Mice, Inbred C57BL; D009856:Oncogene Proteins, Viral / Q000008:administration & dosage* / Q000276:immunology; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000517:prevention & control / Q000821:virology; D053918:Papillomavirus Vaccines / Q000008:administration & dosage* / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D002583:Uterine Cervical Neoplasms / Q000517:prevention & control* / Q000821:virology; D022721:Vaccines, Virosome / Q000008:administration & dosage* / Q000276:immunology; D002578:Uterine Cervical Dysplasia / Q000517:prevention & control* / Q000821:virology
D000914:Antibodies, Viral; D019496:Cancer Vaccines; D015395:Histocompatibility Antigens Class I; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines; D022721:Vaccines, Virosome; C059731:oncogene protein E7, Human papillomavirus type 16