title: Development of a live attenuated antigenic marker classical swine fever vaccine.
abstract: Until recently strategies for controlling Classical Swine Fever Virus (CSFV) involve either prophylactic vaccination or non-vaccination with elimination of infected herds depending on the epidemiological situation of the affected geographical area. Marker vaccines allowing distinction between naturally infected from vaccinated swine could complement "stamping out" measures. Here we developed a double antigenic marker live attenuated CSFV strain FlagT4v obtained by combining two genetic determinants of attenuation. FlagT4v harbors a positive antigenic marker, synthetic Flag(R) epitope, introduced via a 19mer insertion in E1 glycoprotein; and a negative marker resulting from mutations of the binding site of monoclonal antibody WH303 (mAbWH303) epitope in E2 glycoprotein. Intranasal or intramuscular administration of FlagT4v protected swine against virulent CSFV Brescia strain at early (2 or 3 days), and late (28 days) time post-inoculation. FlagT4v induced antibody response in pigs reacted strongly against the Flag(R) epitope but failed to inhibit binding of mAbWH303 to a synthetic peptide representing the WH303 epitope. These results constitute a proof-of-concept for rationally designing a CSFV antigenically marked live attenuated virus.
authors.affiliation: Plum Island Animal Disease Center, USDA/ARS/NAA, Greenport, NY 11944-0848, USA. lauren.holinka@ars.usda.gov
authors.forename: L G
authors.initials: LG
authors.lastname: Holinka
authors.forename: I
authors.initials: I
authors.lastname: Fernandez-Sainz
authors.forename: V
authors.initials: V
authors.lastname: O'Donnell
authors.forename: M V
authors.initials: MV
authors.lastname: Prarat
authors.forename: D P
authors.initials: DP
authors.lastname: Gladue
authors.forename: Z
authors.initials: Z
authors.lastname: Lu
authors.forename: G R
authors.initials: GR
authors.lastname: Risatti
authors.forename: M V
authors.initials: MV
authors.lastname: Borca
mesh_terms: D000281:Administration, Intranasal; D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000032:analysis*; D001483:Base Sequence; D006691:Classical Swine Fever / Q000276:immunology*; D006692:Classical Swine Fever Virus / Q000276:immunology*; D005819:Genetic Markers; D016679:Genome, Viral; D007273:Injections, Intramuscular; D008969:Molecular Sequence Data; D009154:Mutation; D013552:Swine; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics; D014765:Viral Vaccines
chemical_list: D000956:Antigens, Viral; D005819:Genetic Markers; D014613:Vaccines, Attenuated; D014765:Viral Vaccines