Novel viral vaccines for livestock.

Recent advances in our understanding of virulence factors of viruses and the proteins or glycoproteins involved in inducing neutralizing antibodies or cell mediated immunity are forming the foundation for the development of a new generation of viral vaccines. Using bovine herpesvirus as an example, we have identified glycoproteins gB, gC, and gD as important targets for inducing neutralizing antibody responses, with gD being able to induce the highest neutralizing and cellular responses. For subunit vaccine development, the glycoproteins were produced in both prokaryotic and eukaryotic expression systems. Glycoproteins produced in eukaryotic systems were very effective in stimulating a broad range of immune responses in cattle. These glycoproteins were then formulated into effective vaccines that prevented both virus shedding and clinical disease. Herpesviruses also served as an excellent model for the identification and deletion of specific genes which lead to attenuation. In herpesviruses, two major classes of genes can be deleted. Class I includes glycoprotein genes that are nonessential for virus replication in vitro, and Class II includes genes involved in nucleic acid metabolism. these gene deleted regions can then be replaced with genes coding for protective antigens of other pathogens to develop multivalent vaccines in a single vector. Similar approaches are being used for other viruses including vaccinia virus and adenovirus. Finally, we introduced plasmids coding for protective antigens, gB, gC, and gD, into animals and developed immunity to these antigens. This approach has the potential to revolutionize vaccination regimes of the future.