title: Chimeric pestiviruses: candidates for live-attenuated classical swine fever marker vaccines.
abstract: The use of attenuated classical swine fever virus (CSFV) strains as live vaccines is no longer allowed for the control of classical swine fever in Europe, due to the inability to differentiate between infected and vaccinated animals (Differentiating Infected from Vaccinated Animals; DIVA), except as emergency vaccines or as bait vaccines for wild boars. Thus, the establishment of a DIVA vaccine(s) is of pivotal importance for the control of this infectious disease. In this study, recombinant versions of the live-attenuated vaccine strain CSFV Riems were generated by replacing parts of the E2 gene with the corresponding sequence of border disease virus strain Gifhorn. Three cDNA clones were constructed: pRiems-ABC-Gif, pRiems-A-Gif and pRiems-BC-Gif. Infectious particles were obtained from clones pRiems-ABC-Gif and pRiems-BC-Gif only, whereas transfected RNA from clone pRiems-A-Gif behaved like a replicon. Based on its ability to be differentiated in vitro from wild-type CSFV by mAbs, vRiems-ABC-Gif was assessed for immunogenicity and protection against challenge infection in pigs. Before challenge, no CSFV-specific anti-E2 antibodies could be detected with commercial E2-blocking ELISAs in vRiems-ABC-Gif-vaccinated animals, whereas vRiems-vaccinated pigs developed high titres of anti-E2 antibodies, confirming the marker properties of this vaccine candidate. After oral vaccination, only partial protection against challenge infection was observed in the vRiems-ABC-Gif vaccinees, whereas all intramuscularly vaccinated animals and all vRiems-vaccinated animals were fully protected. These experiments suggest that the strategy of exchanging specific antigenic epitopes among pestiviruses is a promising tool for the development of new CSFV marker vaccines.
authors.affiliation: Institute of Virology and Immunoprophylaxis, CH-3147 Mittelhäusern, Switzerland.
authors.forename: Franziska
authors.initials: F
authors.lastname: Wehrle
authors.affiliation: Institute of Virology and Immunoprophylaxis, CH-3147 Mittelhäusern, Switzerland.
authors.forename: Sandra
authors.initials: S
authors.lastname: Renzullo
authors.affiliation: Friedrich-Loeffler-Institut (FLI), Boddenblick 5a, D-17493 Greifswald-Insel Riems, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Faust
authors.affiliation: Friedrich-Loeffler-Institut (FLI), Boddenblick 5a, D-17493 Greifswald-Insel Riems, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Beer
authors.affiliation: Friedrich-Loeffler-Institut (FLI), Boddenblick 5a, D-17493 Greifswald-Insel Riems, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Kaden
authors.affiliation: Institute of Virology and Immunoprophylaxis, CH-3147 Mittelhäusern, Switzerland.
authors.forename: Martin A
authors.initials: MA
authors.lastname: Hofmann
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000918:Antibody Specificity; D018083:Border disease virus / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D006691:Classical Swine Fever / Q000276:immunology / Q000517:prevention & control*; D006692:Classical Swine Fever Virus / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D005814:Genes, Viral / Q000235:genetics*; D006023:Glycoproteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D007273:Injections, Intramuscular; D016865:Reassortant Viruses / Q000276:immunology* / Q000378:metabolism; D013552:Swine; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics; D015678:Viral Structural Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage*
chemical_list: D000914:Antibodies, Viral; D000939:Epitopes; D006023:Glycoproteins; D014613:Vaccines, Attenuated; D015678:Viral Structural Proteins; D014765:Viral Vaccines; C085424:glycoprotein E2, border disease virus