title: Fowlpox virus recombinants expressing HPV-16 E6 and E7 oncogenes for the therapy of cervical carcinoma elicit humoral and cell-mediated responses in rabbits.
abstract: BACKGROUND
  Around half million new cases of cervical cancer arise each year, making the development of an effective therapeutic vaccine against HPV a high priority. As the E6 and E7 oncoproteins are expressed in all HPV-16 tumour cells, vaccines expressing these proteins might clear an already established tumour and support the treatment of HPV-related precancerous lesions.
  
  
  METHODS
  Three different immunisation regimens were tested in a pre-clinical trial in rabbits to evaluate the humoral and cell-mediated responses of a putative HPV-16 vaccine. Fowlpoxvirus (FP) recombinants separately expressing the HPV-16 E6 (FPE6) and E7 (FPE7) transgenes were used for priming, followed by E7 protein boosting.
  
  
  RESULTS
  All of the protocols were effective in eliciting a high antibody response. This was also confirmed by interleukin-4 production, which increased after simultaneous priming with both FPE6 and FPE7 and after E7 protein boost. A cell-mediated immune response was also detected in most of the animals.
  
  
  CONCLUSIONS
  These results establish a preliminary profile for the therapy with the combined use of avipox recombinants, which may represent safer immunogens than vaccinia-based vectors in immuno-compromised individuals, as they express the transgenes in most mammalian cells in the absence of a productive replication.
authors.affiliation: Department of Medical Pharmacology, Università di Milano, Milan, Italy. antonia.radaelli@unimi.it
authors.forename: Antonia
authors.initials: A
authors.lastname: Radaelli
authors.forename: Eleana
authors.initials: E
authors.lastname: Pozzi
authors.forename: Sole
authors.initials: S
authors.lastname: Pacchioni
authors.forename: Carlo
authors.initials: C
authors.lastname: Zanotto
authors.forename: Carlo De Giuli
authors.initials: Cde G
authors.lastname: Morghen
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D002457:Cell Extracts; D045744:Cell Line, Tumor; D002645:Chickens; D005260:Female; D005587:Fowlpox virus / Q000235:genetics*; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D056724:Immunity, Humoral / Q000276:immunology*; D051379:Mice; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D050725:Papillomavirus E7 Proteins / Q000235:genetics*; D011817:Rabbits; D011995:Recombination, Genetic; D012097:Repressor Proteins / Q000235:genetics*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000628:therapy* / Q000821:virology
chemical_list: D002457:Cell Extracts; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16
references.citation: Virology. 1991 Mar;181(1):62-9
references.pmid: 1847269
references.citation: Oncogene. 2008 Mar 6;27(11):1610-7
references.pmid: 17828299
references.citation: J Clin Microbiol. 1998 Feb;36(2):475-80
references.pmid: 9466762
references.citation: Vaccine. 2003 May 16;21(17-18):2052-64
references.pmid: 12706695
references.citation: Arch Med Res. 2009 Aug;40(6):493-8
references.pmid: 19853190
references.citation: J Virol. 2003 Jan;77(2):1551-63
references.pmid: 12502868
references.citation: Virology. 2002 Dec 20;304(2):451-9
references.pmid: 12504584
references.citation: JAMA. 2007 Aug 15;298(7):743-53
references.pmid: 17699008
references.citation: J Infect Dis. 2007 Nov 15;196(10):1438-46
references.pmid: 18008221
references.citation: Expert Rev Vaccines. 2005 Feb;4(1):63-76
references.pmid: 15757474
references.citation: J Immunol. 1992 Apr 15;148(8):2617-21
references.pmid: 1313847
references.citation: Vaccine. 2001 Jun 14;19(27):3652-60
references.pmid: 11395199
references.citation: Infect Agent Cancer. 2006 Nov 08;1:6
references.pmid: 17150135
references.citation: Vaccine. 1995 Nov;13(16):1509-14
references.pmid: 8578834
references.citation: J Immunol. 2002 Jul 1;169(1):350-8
references.pmid: 12077264
references.citation: Vaccine. 1988 Dec;6(6):497-503
references.pmid: 2854338
references.citation: Clin Cancer Res. 2004 May 1;10(9):2954-61
references.pmid: 15131030
references.citation: Virology. 1991 Nov;185(1):251-7
references.pmid: 1656586
references.citation: Hum Pathol. 1988 Jun;19(6):697-704
references.pmid: 2837431
references.citation: J Gen Virol. 1993 Jun;74 ( Pt 6):945-53
references.pmid: 8389809
references.citation: Oncogene. 2009 Feb 5;28(5):762-72
references.pmid: 19015633
references.citation: CMAJ. 2007 Aug 28;177(5):469-79
references.pmid: 17671238
references.citation: Oncogene. 2003 Sep 4;22(38):5938-45
references.pmid: 12955072
references.citation: Clin Dermatol. 1997 Mar-Apr;15(2):275-83
references.pmid: 9167911
references.citation: J Virol. 1990 Feb;64(2):519-26
references.pmid: 2153221
references.citation: Viral Immunol. 2003;16(2):111-21
references.pmid: 12828864
references.citation: J Gen Virol. 1998 May;79 ( Pt 5):1159-67
references.pmid: 9603331
references.citation: Antiviral Res. 2010 Oct;88(1):53-63
references.pmid: 20643163
references.citation: Expert Rev Vaccines. 2008 Sep;7(7):889-93
references.pmid: 18767940
references.citation: Vaccine. 1988 Dec;6(6):466-8
references.pmid: 2854335
references.citation: Vaccine. 1992;10(1):8-9
references.pmid: 1311489
references.citation: Hum Gene Ther. 2008 Apr;19(4):354-64
references.pmid: 18439124
references.citation: J Virol. 2003 Jun;77(11):6093-100
references.pmid: 12743266
references.citation: Expert Opin Biol Ther. 2008 Apr;8(4):421-39
references.pmid: 18352847
references.citation: Oncogene. 1999 Dec 13;18(53):7690-700
references.pmid: 10618709
references.citation: J Virol. 1989 Oct;63(10):4417-21
references.pmid: 2476573
references.citation: J Virol. 2002 Aug;76(15):7616-24
references.pmid: 12097575
references.citation: Vaccine. 2001 Mar 21;19(17-19):2549-56
references.pmid: 11257391
references.citation: J Acquir Immune Defic Syndr (1988). 1991;4(6):641-3
references.pmid: 1673716
references.citation: Vaccine. 2002 Oct 4;20(29-30):3456-64
references.pmid: 12297390
references.citation: J Virol Methods. 2009 Jan;155(1):77-81
references.pmid: 18955084
references.citation: N Engl J Med. 2002 Nov 21;347(21):1645-51
references.pmid: 12444178
references.citation: Virology. 1991 Apr;181(2):572-9
references.pmid: 1707567
references.citation: J Virol. 1985 Jul;55(1):246-50
references.pmid: 2409299
references.citation: Int J Cancer. 1993 Feb 20;53(4):591-6
references.pmid: 8382193
references.citation: J Virol. 1990 Jul;64(7):3151-6
references.pmid: 1693698
references.citation: Lancet. 2006 Apr 15;367(9518):1247-55
references.pmid: 16631880
references.citation: J Virol Methods. 2009 Jun;158(1-2):184-9
references.pmid: 19428588
references.citation: Gene Ther. 2001 Jan;8(2):128-38
references.pmid: 11313782
references.citation: Vaccine. 2006 Aug 31;24 Suppl 3:S3/114-21
references.pmid: 16949998
references.citation: Intervirology. 1994;37(3-4):189-200
references.pmid: 7843930
references.citation: Int J Cancer. 1999 Jun 11;81(6):881-8
references.pmid: 10362134
references.citation: Int J Cancer. 2004 Mar 20;109(2):157-62
references.pmid: 14750163
references.citation: Int J Cancer. 2008 Jan 15;122(2):247-59
references.pmid: 17973257
references.citation: Lancet. 1996 Jun 1;347(9014):1523-7
references.pmid: 8684105
references.citation: Vaccine. 2003 Mar 28;21(13-14):1539-47
references.pmid: 12615451
references.citation: Clin Cancer Res. 2003 Nov 1;9(14):5205-13
references.pmid: 14614000
references.citation: EMBO J. 1989 Dec 1;8(12):3905-10
references.pmid: 2555178
references.citation: Cancer Res. 2003 Sep 15;63(18):6032-41
references.pmid: 14522932