|Loy, J -|
|Gander, Jill -|
|Mogler, Mark -|
|Vander Veen, Ryan -|
|Harris, D -|
|Kamrud, Kurt -|
Submitted to: Virology Journal
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: January 22, 2013
Publication Date: January 28, 2013
Citation: Loy, J.D., Gander, J., Mogler, M., Vander Veen, R., Ridpath, J.F., Harris, D.L., Kamrud, K. 2013. Development and evaluation of a replicon particle vaccine expressing the E2 glycoprotein of bovine viral diarrhea virus (BVDV) in cattle. Virology Journal. 10:35. doi: 10.1186/1743-422x-10-35. Interpretive Summary: Infection with bovine viral diarrhea viruses (BVDV) results in serious economic losses to the dairy and beef industries. While vaccines against BVDV have been available in the U.S. for the past 50 years their use has not resulted in significant decreases in the incident of BVDV infection. The purpose of this research was to develop a vaccine that is safer, has a broader range of protection and has fewer side effects than those presently on the market. Protection against infection with BVDV is the result of the immune system recognizing a BVDV protein called E2. The strategy for the new vaccine tested in this study was to use a defective virus, derived from a type of virus called an Alphavirus, that contained contained the E2 protein. These defective viruses, called replicons, infect cells and make viral proteins but are not able to assemble more viruses that are able to infect cells. When a replicon, containing the E2 protein, infects cells, the immune system is exposed to the E2 protein and a protective immune response is generated. It was shown that the new vaccine resulted in an immune response that protected calves from disease. This approach holds promise for a safe and effective vaccine against BVDV.
Technical Abstract: 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. 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. This is the first experiment to demonstrate that replicon particles can be utilized in a standard prime/boost vaccination strategy in calves against a commercially significant bovine pathogen. This approach holds promise for a safe and effective vaccine against BVDV.