Replication competent strains of vaccinia virus as improved vaccine vectors

Vaccination is a very effective method of preventing illness due to infection by microorganisms. The vaccinating agent used to protect against smallpox has been so effective that it has led to the eradication of the smallpox virus (variola) in the natural world. This vaccinating agent is called vaccinia virus and is used in its live form to vaccinate against smallpox. However, infection with vaccinia virus can result in serious and unintended complications in a small number of vaccinated individuals and, for this reason, smallpox vaccinations were halted after smallpox was declared eradicated from the natural world. Recently, there has been a growing interest in once again vaccinating the population due to the possibility that some terrorist Groups may have acquired stocks of variola that could be used to infect populations at some future time. Additionally, because vaccinia virus is frequently tested as a recombinant vaccine against other infectious agents and against cancer, a safer strain of the virus would decrease the risk of adverse side effects after infection with, vaccinia virus.; Vaccinia virus contains a number of genes that allow it to circumvent the host's immune response, thereby resulting in an increased pathogenic potential. The E3L gene of vaccinia virus encodes a 190 amino acid protein that enables the virus to evade the anti-viral interferon response of the host. Deletions of all or part of this gene from the virus results in decreased pathogenesis of the virus in both immune-competent and immune-compromised animals as outlined in Chapter 1. Despite the decreased pathogenicity of these viral mutants, they retain the ability to protect vaccinated animals against challenge discussed in Chapter 2. In order to describe the mechanisms by which vaccination occurs, immunological studies were undertaken in mice to identify the type and quality of the immune response to these mutant strains of vaccinia virus. These results are presented in Chapter 3. The reduced pathogenicity of these mutant viral strains as well as their ability to effectively vaccinate by the subsequently described immune mechanisms indicates that these mutant viruses may be safer alternatives to the currently used smallpox vaccine.