Pre-clinical immunogenicity and anti-tumour efficacy of a deleted recombinant human papillomavirus type 16 E7 protein.
BACKGROUND
Current vaccination strategies against Human papillomavirus (HPV)-induced ano-genital cancers mostly target E7 from HPV16. However, the oncogenic nature of E7 raises potential human safety issues. Although the modifications abrogating the E7 transforming potential have been well characterized, their effect on E7 immunogenicity has been poorly studied. In this study, we evaluated the vaccine potential of an HPV16 E7 protein deleted from the entire pRb-binding motif.


METHODS
Purified recombinant deleted (E7delta21-26) and wild-type (His6-E7 and E7WT) E7 proteins were studied in pre-clinical mice models.


RESULTS
In C57BL/6 mice, E7delta21-26 formulated with the Quil A adjuvant generated systemic E7-specific cytotoxic T-cell and antibody responses similar to those induced following His6-E7/Quil A and E7WT/Quil A vaccinations. E7delta21-26/Quil A injections efficiently protected animals from challenge with the HPV16-expressing tumours, C3 and TC-1. Moreover, therapeutic vaccination with adjuvant-modified E7 suppressed or significantly decreased C3 tumour outgrowth.


CONCLUSIONS
E7delta21-26 could represent a safe and efficient vaccine candidate against E7-containing tumour cells.
Chimie Biologique, Institut de Biologie et de Médecine Moléculaires, Université Libre de Bruxelles, 6041 Gosselies, Belgium.
Sophie
S
Hallez
Jean-Marc
JM
Brulet
Caroline
C
Vandooren
Frédéric
F
Maudoux
Séverine
S
Thomas
Michel
M
Heinderickx
Alex
A
Bollen
Ruddy
R
Wattiez
Alain
A
Jacquet
D000818:Animals; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D002461:Cell Line, Transformed; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology*; D027383:Papillomaviridae / Q000235:genetics / Q000276:immunology; D050725:Papillomavirus E7 Proteins; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D019496:Cancer Vaccines; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D010446:Peptide Fragments; D011994:Recombinant Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D007371:Interferon-gamma