Development and evaluation of a replicon particle vaccine expressing the E2 glycoprotein of bovine viral diarrhea virus (BVDV) in cattle

Abstract

BackgroundBovine viral diarrhea virus is one of the most significant and costly viral pathogens of cattle worldwide. Alphavirus-derived replicon particles have been shown to be safe and highly effective vaccine vectors against a variety of human and veterinary pathogens. Replicon particles are non-propagating, DIVA compatible, and can induce both humoral and cell mediated immune responses. This is the first experiment to demonstrate that Alphavirus-based replicon particles can be utilized in a standard prime/boost vaccination strategy in calves against a commercially significant bovine pathogen.FindingsReplicon particles that express bovine viral diarrhea virus sub-genotype 1b E2 glycoprotein were generated and expression was confirmed in vitro using polyclonal and monoclonal antibodies specific to E2. Vaccine made from particles was generated in Vero cells and administered to BVDV free calves in a prime/boost regimen at two dosage levels. Vaccination resulted in neutralizing antibody titers that cross-neutralized both type 1 and type 2 BVD genotypes following booster vaccination. Additionally, high dose vaccine administration demonstrated some protection from clinical disease and significantly reduced the degree of leukopenia caused by viral infection.ConclusionsReplicon particle vaccines administered in a prime/boost regimen expressing BVDV E2 glycoprotein can induce cross-neutralizing titers, reduce leukopenia post challenge, and mitigate clinical disease in calves. This strategy holds promise for a safe and effective vaccine to BVDV.

The Molecular Biology of Pestiviruses

“…Thus, the trigger for the immune system is probably not very strong. Nevertheless, induction of protective immunity has been successfully demonstrated in stringent challenge models in several cases (Frey et al, 2006;Loy et al, 2013;Maurer et al, 2005;Sun et al, 2011;Yang et al, 2012;Zemke, Koenig, Mischkale, Reimann, & Beer, 2010). However, it is not yet clear whether a single vaccination with a replicon can consistently prevent fetal infection in a pregnant animal.…”

Bovine Viral Diarrhea Virus Infections

“…7,125,148 Due to the antigenic variability, there is potential for a lack of cross-protection against wildtype BVDV viruses, even though cross-neutralization studies have shown reactivity to differing genotypes. 93 Since disease due to BVDV remains widespread, additional measures beyond vaccination are needed.…”

Serologic and Virologic Investigation of BHV-1, BVDV and BHV-4 in Cattle with Metritis

“…BVDV and BHV-1 are most important and costly viral pathogens of cattle worldwide [19] that mainly associated with reproductive problems and increased abortion [3,10]. There were no antibody and antigen positive animals for BHV-1 infection ( Table 1).…”