Development of therapeutic vaccine against HPV-16 induced tumor- influence of E7 antigen modification on cell madiated immune response

Conclusions We constructed the vaccines carrying IIPV-16 E7 antigen based on .B. pertussisCyaA toxin We introduced ELISPOT and MHC-I totaÍner assays for testing of cell-mediarcdimmrmeresponsein themousemodel We tested cell-mediated immune response following immunization with differentkinds of thevaccinescarryingthemodifiedHPV-16 E7 antigen: o Recombinantadenylďe cyclase toxoid CyaA336IE7 is able to induce E7 specific CDE- cellular immuneresponsein mice and proteď them againstTC-l firmorgrowth o Some DNA vaccines carying the E7 genefusď to anothergeneare able to induoe betteranti-tumorimmuneresponsethan non-modified E7 genein mice @NA vaccinesevďuated accordingto themagpitude of CTL responseinduced: ETCTGG.GUS > ETGGGHSP, ETHSP >> cP-E7 >E7) o Fusion of E7 with W hemagglutininleadsto cell-surfaceexpressionof E7 and following vaccinďion with W.E7.HA it induces Th-2 polarized immuner€spons€ type ďong with the absenceof anti.tumor Th-l response o Co-expression of IL-12 from double recombinant vaccinia virus (W.IL-l2-sig/E7|LAI\D) reducesCD8- cellular immuniý inducedby Sig/E7lLAMP o Immunization with dendritic cells transducedby rW improves the efficacy of rW vaccination o Combined immunization increases vaccination effectiveness (CyaA336/E7+MVA- Sig/E7lLAMP, DNA-SigETGGG/LAMP+cellular vaccine) I