Pokorná, D.; Čeřovská, Noemi; Šmahel, M.; Moravec, Tomáš; Ludvíková, V.; Machková, J.; Synková, Helena; Dušková, M.; Hozák, P.; Velemínský, Jiří
ONCOLOGY REPORTS 14 [4]: 1045-1053, 2005

Keywords: human papillomavirus; E7; virus-like particles
Abstract: Vaccine strategies for the treatment of humen papillomavirus-induced cervical cancer are based maily on the humen papillomavirus 16 E7 (HPV 16 E7) oncoprotein. The immunogenicity of the E7 gene has been enhanced by its fusion to many different genes. Here, we linked a short sequence coding for the E7 peptide (aa 44-60) containing immunodominant epitopes for B and T cells to the 3´ end of the gene coding for the whole coat protein (CP) of the potyvirus, potato virus A, and its deleted form (CPdel) with a short C-terminal deletion of 5 amino acids (LGVKG). CP-E7 and CPdel-E7 fusion proteins, just like CP alone, spotaneously assembled into virus-like particles in both procaryotic and eucaryotic cells. The CP-E7 and CPdel-7 induced slightly stronger E7-specific cytotoxin T-lymphocyte response than the whole E7 gene, although they were still lower than those elicited by the previously consctructed fusion gene, Sig/E7GGG/LAMP-1. The E-7 and CP-specific antibody responses were not detected in mice vaccinated with CP-E7 and CPdel-E7 fusion genes. The CP-E7 and CPdel-E7 fusion genes protected mise against the development of tumors induced by TC-1 cells producing the E7 antigen and were also effetive in the therapeutic setting, i.e. when the wacciation was performed after tumor cell administration. Their antitumor effect were comparable to those of the whole E7 gene and Sig/E7GGG/LAMP-1 fusion gene. There were no relevant difference between immune respopnses elicited by CP-E7 and CPdel-E7 DNA vaccination.
DOI: IEB authors: Noemi Čeřovská, Tomáš Moravec, Helena Synková