Novel Vaccine Strategies to Prevent Herpes Simplex Virus Infection

Herpes simplex virus, which infects a majority of the population, remains a significant human pathogen for which no effective vaccine exists. Despite decades of intensive research, this virus has resisted numerous classical and cutting edge approaches. We can only hope that additional research into new vaccines ideas as well as the fundamentals of how the virus interacts with the immune system will someday lead to the design of an effective vaccine. The first part of this dissertation focuses on the virus and how it interacts with various immune cells in the body. HSV-1 exerts a number of influences on a number of key immune cells, especially dendritic cells. The overview goes on to fully describe these interactions, the nature of the immune response generated to the virus, as well as part and possible future vaccine strategies. The second part explores the use of hsp70 and peptide as an effective vaccine candidate in the neonate, in which infection can lead to life threatening situations. Results suggest that hsp70 is an effective adjuvant in neonates. The third section examines the use of hsp70 and peptide as a mucosal adjuvant in adult mice. These data also demonstrate that hsp70 can act as an potent mucosal adjuvant. The final section explores utilizing an anti-DNA antibody to enhance targeting of plasmid DNA to antigen presenting cells in order to improve immune responses. Results indicate that anti-DNA antibody enhances immune responses to plasmid encoded antigen. In all, we hope that these novel vaccine approaches may one day be used in humans to induce protective immune responses to HSV-1.