title: Discrimination within epitope specific antibody populations against Classical swine fever virus is a new means of differentiating infection from vaccination.
abstract: Serological differentiation between infection and vaccination depends on the detection of pathogen specific antibodies for an epitope that is modified or lacking in a vaccine. Here we describe a new assay principle that is based on differences in the binding properties of epitope specific antibodies. C-DIVA is a potent Classical swine fever vaccine candidate that differs from the parental C-strain life attenuated vaccine in the highly immunogenic TAVSPTTLR epitope by the deletion of two and the mutation of one amino acid (TAGSΔΔTLR). We show that C-DIVA vaccination elicits antibodies with high affinity for both the TAGSΔΔTLR and TAVSPTTLR epitope, whereas infection elicits only TAVSPTTLR specific antibodies. Differentiation is achieved with a double competition assay with negative selection for antibodies with affinity for the TAGSΔΔTLR epitope followed by positive selection for antibodies with affinity for the TAVSPTTLR epitope. Our findings add a new strategy for the development of marker vaccines and their accompanying discrimination assays and offer an alternative to the devastating stamping out policy for Classical swine fever.
authors.affiliation: Discovery & Technology Vaccine Analysis, MSD Animal Health, Boxmeer, The Netherlands. Electronic address: urs.bruderer@merck.com.
authors.forename: Urs
authors.initials: U
authors.lastname: Bruderer
authors.affiliation: Discovery & Technology Vaccine Analysis, MSD Animal Health, Boxmeer, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: van de Velde
authors.affiliation: Discovery & Technology Expression, MSD Animal Health, Boxmeer, The Netherlands.
authors.forename: Inge
authors.initials: I
authors.lastname: Frantzen
authors.affiliation: Institute of Chemistry and Biochemistry, Free University of Berlin, Berlin, Germany.
authors.forename: Francesca
authors.initials: F
authors.lastname: De Bortoli
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D000915:Antibody Affinity; D000918:Antibody Specificity; D006691:Classical Swine Fever / Q000276:immunology* / Q000517:prevention & control; D006692:Classical Swine Fever Virus / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D013552:Swine; D014765:Viral Vaccines / Q000276:immunology* / Q000494:pharmacology
chemical_list: D000914:Antibodies, Viral; D000939:Epitopes; D014765:Viral Vaccines
keywords: Classical swine fever; Discrimination assay; Immune response; Marker vaccine