Herpesvirus vaccines

Most animals and humans are pl one to infection with at least one type of herpesvirus. In some cases the infection is more of an irritant than one of economics or medical significance, however, in many other cases, infections by herpesviruses do cause significant discomfort and even death. Thus, many individuals have attempted to develop conventional vaccines to modulate these infections. Recent advances in our understanding of virulence factors of herpesviruses and the proteins or glycoproteins involved in inducing neutralizing antibodies and cell-mediated immunity are forming the foundation for the development of a new generation of vaccines. The present review summarizes our understanding of the immunology of alphaherpesviruses combined with our understanding of viral replication and proteins involved in inducing protection. Using subunit vaccine approaches, it has been possible to demonstrate that an individual glycoprotein can induce immune responses which are able to neutralize the virus as well as reduce clinical disease. Based on these studies, it has been possible to directly transfer the gene encoding the protective protein into animals which then produce sufficient quantities of the gene product to induce immunity. This approach has the possibility of supplanting conventional vaccination approaches to herpes infections. In addition to subunit or polynucleotide vaccination, live 'marked vaccines' are being developed, especially for use in animals. Development of 'marked vaccines' in animals is based primarily on the observation that deletion of specific genes results in attenuation of the virus as well as providing an opportunity to differentiate animals immunized with these vaccines from latent carriers of the infection. Deletion in two different classes of genes have been used for these investigations. Class I includes glycoprotein genes that are non-essential for replication in vitro and Class II includes genes involved in nucleic acid metabolism. These gene-deleted regions result in attenuation of the virus without altering their ability to induce protective immune responses. These different approaches to vaccination of humans and animals against herpes infections are described.