Immunity in the female genital tract after intravaginal vaccination of mice with an attenuated strain of herpes simplex virus type 2

Abstract

Herpes simplex virus type 2 is a common human venereal pathogen which causes lethal neurological illness after intravaginal inoculation into BALB/cJ mice. To investigate whether an attenuated, nonlethal strain of this virus would confer immunity after inoculation of mice, a strain containing a partial deletion of the thymidine kinase gene, which is necessary for viral replication and spread in sensory ganglia, was constructed. Unlike its wild-type counterpart, this deletion-containing strain of herpes simplex virus type 2 caused mild clinical disease and was not lethal when studied in an age-dependent murine model of intravaginal infection. After intravaginal infection, the deletion-containing strain could not be isolated from sensory ganglia at a time when wild-type virus was abundant. Of greater significance, intravaginal inoculation with the deletion-containing strain rendered mice completely resistant to rechallenge with a 10-fold LD50 of wild-type virus. Evidently, a strain of herpes simplex virus type 2 containing a deletion of the thymidine kinase gene will be useful in studying the cellular basis of mucosal immunity in the genital tract.