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Open Access Short report

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

John Dustin Loy15*, Jill Gander1, Mark Mogler12, Ryan Vander Veen1, Julia Ridpath3, Delbert Hank Harris124 and Kurt Kamrud12

Author Affiliations

1 Harrisvaccines, Inc, 1102 Southern Hills Dr. Suite 101, Ames, IA 50010, USA

2 Department of Animal Science, Iowa State University, Kildee Hall, Ames, IA 50011, USA

3 United States Department of Agriculture, Agricultural Research Service, Ruminant Diseases and Immunology Research Unit, Ames, IA 50010, USA

4 Department of Veterinary Diagnostic and Preventive Medicine, Iowa State University, Ames, IA 50011, USA

5 University of Nebraska-Lincoln, Department of Veterinary and Biomedical Sciences, Lincoln, NE 68502-0907, USA

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Virology Journal 2013, 10:35  doi:10.1186/1743-422X-10-35

Published: 28 January 2013

Abstract

Background

Bovine 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.

Findings

Replicon 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.

Conclusions

Replicon 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.

Keywords:
BVD; Bovine viral diarrhea virus; Alphavirus replicon; Replicon particle; Vaccine