title: Chemokine binding protein vCCI attenuates vaccinia virus without affecting the cellular response elicited by immunization with a recombinant vaccinia vector carrying the HPV16 E7 gene.
abstract: Viral CC chemokine inhibitor (vCCI) of the clone P13 vaccinia virus (VACV) strain PRAHA lacks eight amino acids in the signal peptide sequence. To study the influence of vCCI on virus biology, a virus with the vCCI gene coding for a prolonged signal sequence was prepared. We found that secreted vCCI attenuated the virus in vivo, and that it correlated with decreased levels of RANTES, eotaxin, TARC, and MDC in the blood in comparison with the parental virus. We determined the influence of vCCI on the CTL response against VACV E3((140-148)) (VGPSNSPTF) and HPV16 E7((49-57)) (RAHYNIVTF) H-2D(b)-restricted epitopes. The examination of the specific CTL response elicited by immunization with the recombinant VACV-expressing tumor-associated HPV16 E7 antigen by IFN-γ ELISPOT showed that the immunogenicity of the recombinant VACV-producing secretory vCCI was similar to that of the parent virus or deletion mutant in the C23L/B29R locus. Immunization with the secretory vCCI-producing recombinant virus has a lower therapeutic anti-tumor effect against TC-1 tumors. Viral CCI downregulated the E7-specific response induced by gene gun immunization with the DNA vaccines pBSC-SigE7 LAMP and pBSC-vCCI. We also observed that the immune response against vCCI elicited by the DNA vaccine did not affect the multiplication of VACV in vivo.
authors.affiliation: Department of Experimental Virology, Institute of Hematology and Blood Transfusion, Prague, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Gabriel
authors.forename: Katarina
authors.initials: K
authors.lastname: Babiarova
authors.forename: Kamila
authors.initials: K
authors.lastname: Zurkova
authors.forename: Jitka
authors.initials: J
authors.lastname: Krystofova
authors.forename: Petr
authors.initials: P
authors.lastname: Hainz
authors.forename: Luda
authors.initials: L
authors.lastname: Kutinova
authors.forename: Sarka
authors.initials: S
authors.lastname: Nemeckova
mesh_terms: D051722:ADAM Proteins / Q000097:blood; D000818:Animals; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D054414:Chemokine CCL17 / Q000097:blood; D018946:Chemokine CCL5 / Q000097:blood; D019742:Chemokines, CC / Q000037:antagonists & inhibitors* / Q000097:blood*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D050725:Papillomavirus E7 Proteins / Q000235:genetics* / Q000276:immunology; D017384:Sequence Deletion; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D025521:Tumor Suppressor Proteins / Q000097:blood; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics* / Q000276:immunology* / Q000472:pathogenicity; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D019496:Cancer Vaccines; D054414:Chemokine CCL17; D018946:Chemokine CCL5; D019742:Chemokines, CC; D050725:Papillomavirus E7 Proteins; D025521:Tumor Suppressor Proteins; D014614:Vaccines, Synthetic; D014764:Viral Proteins; D014765:Viral Vaccines; C059731:oncogene protein E7, Human papillomavirus type 16; D051722:ADAM Proteins; C090222:ADAM11 protein, human