Abstract
Marker or DIVA (differentiation of infected from vaccinated animals) vaccines are beneficial tools for the eradication of animal diseases in regions with a high prevalence of the designated disease. Bovine viral diarrhea virus (BVDV)-1 (syn. Pestivirus A) is a flavivirus that infects predominantly cattle resulting in major economic losses. An increasing number of countries have implemented BVDV eradication programs that focus on the detection and removal of persistently infected cattle. No efficient marker or DIVA vaccine is yet commercially available to drive the eradication success, to prevent fetal infection and to allow serological monitoring of the BVDV status in vaccinated farms. Bungowannah virus (BuPV, species Pestivirus F), a related member of the genus Pestivirus with a restricted prevalence to a single pig farm complex in Australia, was chosen as the genetic backbone for a marker vaccine candidate. The glycoproteins E1 and E2 of BuPV were substituted by the heterologous E1 and E2, which are major immunogens, of the BVDV-1 strain CP7. In addition, the candidate vaccine was further attenuated by the introduction of a deletion within the Npro protein coding sequence, a major type I interferon inhibitor. Immunization of cattle with the chimeric vaccine virus BuPV_ΔNpro_E1E2 CP7 (modified live or inactivated) followed by a subsequent experimental challenge infection confirmed the safety of the prototype strain and provided a high level of clinical protection against BVDV-1. The serological discrimination of vaccinated cattle could be enabled by the combined detection of BVDV-1 E2- in the absence of both BVDV NS3- and BVDV Erns-specific antibodies. The study demonstrates for the first time the generation and application of an efficient BVDV-1 modified double marker vaccine candidate that is based on the genetic background of BuPV accompanied by commercially available serological marker ELISA systems.
Highlights
IntroductionThe successful development and application of a chimeric marker vaccine in combination with a DIVA (differentiation of infected from vaccinated animals) test strategy has been approved for many economically important animal pathogens such as bovine herpes virus type 1 (BoHV-1), suid herpesvirus type 1
The successful development and application of a chimeric marker vaccine in combination with a DIVA test strategy has been approved for many economically important animal pathogens such as bovine herpes virus type 1 (BoHV-1), suid herpesvirus type 1
The application of the pestivirus BuPV as the genetic backbone for the design of a Bovine viral diarrhea virus (BVDV)-1 double marker vaccine and the substitution of BuPV_E1E2 with BVDV-1_E1E2 resulted in the induction of a robust immune response that protected from clinical disease after BVDV-1 challenge infection
Summary
The successful development and application of a chimeric marker vaccine in combination with a DIVA (differentiation of infected from vaccinated animals) test strategy has been approved for many economically important animal pathogens such as bovine herpes virus type 1 (BoHV-1), suid herpesvirus type 1 Aujeszky’s disease virus [ADV] or pseudorabies virus [PRV]) and Pestivirus C The serological DIVA test strategy encompasses the implementation of differentiating serology tests (e.g., ELISAs) that clearly discriminate between antibodies acquired by field infection and vaccination. The genus Pestivirus of the Flaviviridae family encompasses a number of pathogen species of great economic importance [5] including CSFV and bovine viral diarrhea virus types 1 and 2 (BVDV-1, BVDV-2). New members of the genus Pestivirus have been found in recent years within a broad range of mammalian hosts—from livestock, rodents to bats and harbor porpoise [6,7,8,9,10,11]
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