Viral recombinant vaccines to the E6 and E7 antigens of HPV-16.

Most cancerous lesions of the uterine cervix are linked to persistent infections with human papillomaviruses (HPV), most notably HPV-16 or -18. Vaccine-induced immune responses to the HPV early antigens E6 and E7, which contribute to cell transformation and are thus expressed in these cervical cancers, could potentially eradicate malignant cells. We generated recombinant vaccines based on E1-deleted adenovirus human strain 5 or on vaccinia virus strain Copenhagen expressing either the E6 or E7 oncoproteins of HPV-16. The different vaccines were compared in two experimental mouse tumor models employing Balb/c or C57Bl/6 mice. Data presented here demonstrate that depending on the model either CD4(+) or CD8(+) T cells provide protection to tumor cell challenge, resulting in striking differences in the efficacy of the four vaccines under investigation.

[1]  M. Feltkamp,et al.  Peptide Vaccination with an Anchor‐Replaced CTL Epitope Protects Against Human Papillomavirus Type 16‐Induced Tumors Expressing the Wild‐Type Epitope , 1998, Journal of immunotherapy.

[2]  D. Pardoll,et al.  Antigen‐specific immunotherapy for murine lung metastatic tumors expressing human papillomavirus type 16 E7 oncoprotein , 1998, International journal of cancer.

[3]  R. Reichman,et al.  Isolation and Propagation of Human Papillomavirus Type 16 in Human Xenografts Implanted in the Severe Combined Immunodeficiency Mouse , 1998, Journal of Virology.

[4]  R. Tigelaar,et al.  Intracutaneous vaccination of rabbits with the E6 gene of cottontail rabbit papillomavirus provides partial protection against virus challenge. , 1998, Vaccine.

[5]  R. Offringa,et al.  Immunization with human papillomavirus type 16 (HPV16) oncoprotein-loaded dendritic cells as well as protein in adjuvant induces MHC class I-restricted protection to HPV16-induced tumor cells. , 1998, Cancer research.

[6]  J. Altman,et al.  Counting antigen-specific CD8 T cells: a reevaluation of bystander activation during viral infection. , 1998, Immunity.

[7]  J. McCann Texas center studies research alternative treatments. , 1997, Journal of the National Cancer Institute.

[8]  M. Ozbun,et al.  Synthesis of infectious human papillomavirus type 18 in differentiating epithelium transfected with viral DNA , 1997, Journal of virology.

[9]  G. Fleuren,et al.  Tumor Eradication by Wild-type p53-specific Cytotoxic T Lymphocytes , 1997, The Journal of experimental medicine.

[10]  H. Rammensee,et al.  Specificity of human cytotoxic T lymphocytes induced by a human papillomavirus type 16 E7-derived peptide. , 1997, The Journal of general virology.

[11]  S. Stacey,et al.  A recombinant vaccinia virus encoding human papillomavirus types 16 and 18, E6 and E7 proteins as immunotherapy for cervical cancer , 1996, The Lancet.

[12]  Z. Xiang,et al.  A replication-defective human adenovirus recombinant serves as a highly efficacious vaccine carrier. , 1996, Virology.

[13]  S. Stacey,et al.  Priming in vivo and quantification in vitro of class I MHC-restricted cytotoxic T cells to human papilloma virus type 11 early proteins (E6 and E7) using immunostimulating complexes (ISCOMs). , 1996, Vaccine.

[14]  H. Ertl,et al.  Immune responses to viral antigens versus transgene product in the elimination of recombinant adenovirus-infected hepatocytes in vivo. , 1996, Gene therapy.

[15]  F. Guarnieri,et al.  Treatment of established tumors with a novel vaccine that enhances major histocompatibility class II presentation of tumor antigen. , 1996, Cancer research.

[16]  Z. Xiang,et al.  Immune effector mechanisms required for protection to rabies virus. , 1995, Virology.

[17]  H. Ertl,et al.  Cellular and humoral immune responses to viral antigens create barriers to lung-directed gene therapy with recombinant adenoviruses , 1995, Journal of virology.

[18]  C. Hsieh,et al.  T cell genetic background determines default T helper phenotype development in vitro , 1995, The Journal of experimental medicine.

[19]  I. Penn The effect of immunosuppression on pre-existing cancers. , 1993, Transplantation.

[20]  A. Bradley,et al.  Multiple defects of immune cell function in mice with disrupted interferon-gamma genes. , 1993, Science.

[21]  K Inaba,et al.  Dendritic cells exposed to human immunodeficiency virus type-1 transmit a vigorous cytopathic infection to CD4+ T cells. , 1992, Science.

[22]  C. Silverman,et al.  Liposomal malaria vaccine in humans: a safe and potent adjuvant strategy. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[23]  A. Levine,et al.  p53 alteration is a common event in the spontaneous immortalization of primary BALB/c murine embryo fibroblasts. , 1991, Genes & development.

[24]  H. Hausen Viruses in human cancers , 1991 .

[25]  K. Rajewsky,et al.  Generation and analysis of interleukin-4 deficient mice. , 1991, Science.

[26]  R. Young,et al.  Humoral and cell-mediated immune responses to live recombinant BCG–HIV vaccines , 1991, Nature.

[27]  M. Lindstrom,et al.  Carcinoma induction following direct in situ transfer of v-Ha-ras into rat mammary epithelial cells using replication-defective retrovirus vectors. , 1991, Cancer research.

[28]  N. Christensen,et al.  The open reading frame L2 of cottontail rabbit papillomavirus contains antibody-inducing neutralizing epitopes. , 1991, Virology.

[29]  R. Lathe,et al.  Immunization against human papillomavirus type 16 tumor cells with recombinant vaccinia viruses expressing E6 and E7. , 1991, Virology.

[30]  L. Chen,et al.  Human papillomavirus type 16 nucleoprotein E7 is a tumor rejection antigen. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[31]  R. Jaenisch,et al.  β2-Microglobulin deficient mice lack CD4−8+ cytolytic T cells , 1990, Nature.

[32]  A. Levine,et al.  Association of human papillomavirus types 16 and 18 E6 proteins with p53. , 1990, Science.

[33]  M. Perkus,et al.  Cloning and expression of foreign genes in vaccinia virus, using a host range selection system , 1989, Journal of virology.

[34]  R. Chanock,et al.  Role of early region 3 (E3) in pathogenesis of adenovirus disease. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[35]  K. Münger,et al.  The human papilloma virus-16 E7 oncoprotein is able to bind to the retinoblastoma gene product. , 1989, Science.

[36]  E. Beachey,et al.  Protective immunity evoked by oral administration of attenuated aroA Salmonella typhimurium expressing cloned streptococcal M protein , 1988, The Journal of experimental medicine.

[37]  D. Cosman,et al.  Stably transmitted triple-promoter retroviral vectors and their use in transformation of primary mammalian cells , 1988, Molecular and cellular biology.

[38]  B. Morein,et al.  The iscom antigen-presenting system , 1988, Nature.

[39]  D. Galloway,et al.  Identification of the E5 open reading frame of human papillomavirus type 16 , 1988, Journal of virology.

[40]  B. Moss,et al.  Vaccinia virus expression vector: coexpression of beta-galactosidase provides visual screening of recombinant virus plaques , 1985, Molecular and cellular biology.

[41]  R. Zaino,et al.  Morphological transformation in vivo of human uterine cervix with papillomavirus from condylomata acuminata , 1985, Nature.

[42]  S. Suhai,et al.  Human papillomavirus type 16 DNA sequence. , 1985, Virology.

[43]  Wolfgang Mayer,et al.  Structure and transcription of human papillomavirus sequences in cervical carcinoma cells , 1985, Nature.

[44]  P. Howley,et al.  Bovine papillomavirus contains multiple transforming genes. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[45]  R. Lathe,et al.  Protection from rabies by a vaccinia virus recombinant containing the rabies virus glycoprotein gene. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[46]  H. Ertl,et al.  Characteristics and functions of Sendai virus-specific T-cell clones , 1984, Journal of virology.

[47]  H. Ertl,et al.  Sendai virus-specific T-cell clones: induction of cytolytic T cells by an anti-idiotypic antibody directed against a helper T-cell clone. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[48]  F. Graham,et al.  Characteristics of a human cell line transformed by DNA from human adenovirus type 5. , 1977, The Journal of general virology.

[49]  H. Mcdevitt,et al.  Histocompatibility-linked immune response genes. , 1972, Science.