Fowlpox virus recombinants expressing HPV-16 E6 and E7 oncogenes for the therapy of cervical carcinoma elicit humoral and cell-mediated responses in rabbits.
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.
Radaelli
Antonia
A
Department of Medical Pharmacology, Università di Milano, Milan, Italy. antonia.radaelli@unimi.it
Pozzi
Eleana
E
Pacchioni
Sole
S
Zanotto
Carlo
C
Morghen
Carlo De Giuli
Cde G
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
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
Virology. 1991 Mar;181(1):62-9
1847269
Oncogene. 2008 Mar 6;27(11):1610-7
17828299
J Clin Microbiol. 1998 Feb;36(2):475-80
9466762
Vaccine. 2003 May 16;21(17-18):2052-64
12706695
Arch Med Res. 2009 Aug;40(6):493-8
19853190
J Virol. 2003 Jan;77(2):1551-63
12502868
Virology. 2002 Dec 20;304(2):451-9
12504584
JAMA. 2007 Aug 15;298(7):743-53
17699008
J Infect Dis. 2007 Nov 15;196(10):1438-46
18008221
Expert Rev Vaccines. 2005 Feb;4(1):63-76
15757474
J Immunol. 1992 Apr 15;148(8):2617-21
1313847
Vaccine. 2001 Jun 14;19(27):3652-60
11395199
Infect Agent Cancer. 2006 Nov 08;1:6
17150135
Vaccine. 1995 Nov;13(16):1509-14
8578834
J Immunol. 2002 Jul 1;169(1):350-8
12077264
Vaccine. 1988 Dec;6(6):497-503
2854338
Clin Cancer Res. 2004 May 1;10(9):2954-61
15131030
Virology. 1991 Nov;185(1):251-7
1656586
Hum Pathol. 1988 Jun;19(6):697-704
2837431
J Gen Virol. 1993 Jun;74 ( Pt 6):945-53
8389809
Oncogene. 2009 Feb 5;28(5):762-72
19015633
CMAJ. 2007 Aug 28;177(5):469-79
17671238
Oncogene. 2003 Sep 4;22(38):5938-45
12955072
Clin Dermatol. 1997 Mar-Apr;15(2):275-83
9167911
J Virol. 1990 Feb;64(2):519-26
2153221
Viral Immunol. 2003;16(2):111-21
12828864
J Gen Virol. 1998 May;79 ( Pt 5):1159-67
9603331
Antiviral Res. 2010 Oct;88(1):53-63
20643163
Expert Rev Vaccines. 2008 Sep;7(7):889-93
18767940
Vaccine. 1988 Dec;6(6):466-8
2854335
Vaccine. 1992;10(1):8-9
1311489
Hum Gene Ther. 2008 Apr;19(4):354-64
18439124
J Virol. 2003 Jun;77(11):6093-100
12743266
Expert Opin Biol Ther. 2008 Apr;8(4):421-39
18352847
Oncogene. 1999 Dec 13;18(53):7690-700
10618709
J Virol. 1989 Oct;63(10):4417-21
2476573
J Virol. 2002 Aug;76(15):7616-24
12097575
Vaccine. 2001 Mar 21;19(17-19):2549-56
11257391
J Acquir Immune Defic Syndr (1988). 1991;4(6):641-3
1673716
Vaccine. 2002 Oct 4;20(29-30):3456-64
12297390
J Virol Methods. 2009 Jan;155(1):77-81
18955084
N Engl J Med. 2002 Nov 21;347(21):1645-51
12444178
Virology. 1991 Apr;181(2):572-9
1707567
J Virol. 1985 Jul;55(1):246-50
2409299
Int J Cancer. 1993 Feb 20;53(4):591-6
8382193
J Virol. 1990 Jul;64(7):3151-6
1693698
Lancet. 2006 Apr 15;367(9518):1247-55
16631880
J Virol Methods. 2009 Jun;158(1-2):184-9
19428588
Gene Ther. 2001 Jan;8(2):128-38
11313782
Vaccine. 2006 Aug 31;24 Suppl 3:S3/114-21
16949998
Intervirology. 1994;37(3-4):189-200
7843930
Int J Cancer. 1999 Jun 11;81(6):881-8
10362134
Int J Cancer. 2004 Mar 20;109(2):157-62
14750163
Int J Cancer. 2008 Jan 15;122(2):247-59
17973257
Lancet. 1996 Jun 1;347(9014):1523-7
8684105
Vaccine. 2003 Mar 28;21(13-14):1539-47
12615451
Clin Cancer Res. 2003 Nov 1;9(14):5205-13
14614000
EMBO J. 1989 Dec 1;8(12):3905-10
2555178
Cancer Res. 2003 Sep 15;63(18):6032-41
14522932