Genetic Engineering and Properties of Novel Herpes Simplex Viruses for Use as Potential Vaccines and as Vectors of Foreign Genes

Abstract

The pathology associated with viral infections as well as the attempts to prevent them are closely dependent on the biology of virus-host interactions. A unique feature of herpes simplex viruses 1 and 2 (HSV-1 and HSV-2) is that, in the course of the primary infection, the viruses multiply at the portal of entry, infect sensory or autonomic nerve endings, ascend through the axon to the neuronal nucleus and establish a latent infection that is shielded from the immune defenses of the host. In a significant fraction of infected individuals, the latent viruses are reactivated by a variety of stimuli and cause clinically discernible lesions. Indeed, most of the morbidity associated with HSV is the result of such recrudescences. Prevention of morbidity caused by HSV, unlike that caused by other viruses, requires blocking the establishment of latency. Inasmuch as establishment of latency results from multiplication at the portal of entry, such prevention requires a state of immunity induced by immunization that is potent enough to preclude this initial multiplication, a very tall order. On the grounds that inactivated or subunit vaccines are not likely to generate both the required duration and level of immunity, we chose to construct a live attenuated HSV vaccine by the techniques of genetic engineering described in detail elsewhere (Roizman and Jenkins, 1985).