Development of Recombinant HSV-Based Vaccine Vectors.

Herpes simplex virus (HSV) causes significant morbidity on the human population through such clinical syndromes as cold sores, genital herpes, herpes stromal keratitis, and encephalitis. Attempts to generate efficacious vaccines to date have failed. We have recently described the use of a conditionally replication-competent HSV-1 vector to immunize mice against a lethal challenge of HSV-1. The unique feature of this vaccine vector is that its replication is tightly controlled and can only occur in the presence of local heat and the presence of a small molecule inducer (an antiprogestin). This gives it the safety advantage of a replication-defective vaccine vector as well as the advantage of a replication-competent vector in that it is able to stimulate innate and adaptive aspects of the immune response in a natural context that a replication-defective vector cannot. In this chapter we provide a brief overview of HSV vaccines followed by the methodology used to propagate and utilize replication-conditional HSV vectors as vaccines.