Vaccinia Recombinants as Vaccine Vectors

Abstract

The advent of recombinant DNA technology has allowed the identifiGation and cloning of genes coding for specific proteins. A significant portion of the focus has centered on genes coding for important surface antigens of infectious agents. The ability to genetically engineer these genes for expression in a variety of vector systems has raised the possibility of utilizing such expression vectors in the immunization of human and animal populations. Bacterial, yeast and viral expression vectors have been described. Antigens produced in vitro by the engineered vector can be purified and administered as subunit vaccines. Alternatively, the vector can be constructed as a live recombinant vaccine to synthesize the antigens during infection of the vaccinee. Both modes of antigen delivery have advantages and disadvantages and therefore, determination of which means is best employed must be decided individually for each antigen. Regardless of which mode is exploited, both safety and efficacy must be rigorously proven. Immunization with infectious viral vectors carrying one or more heterologous genes have been remarkably successful in experimental animal models. These studies have employed adenovirus (1-3), herpes virus (4, 5) and vaccinia virus (6,7) vectored antigens. Vaccinia virus has been the most widely utilized viral vector for the study of foreign gene expression and immunogenicity of the resulting protein. This is due in part to the ease wi~h which vaccinia recombinants containing large pieces of foreign DNA can be constructed. Thus, a considerable body of data has accrued on the utility of vaccinia as an experimental vaccine vector. Taken together with the enormous experience gained during the many years of immunization with vaccinia during the eradication of smallpox, vaccinia virus has vaulted to the forefront in the development of virus-vectored vaccines.