IMMUNIZATION WITH A REPLICATION-DEFICIENT MUTANT OF HERPES-SIMPLEX VIRUS TYPE-1 (HSV-1) INDUCES A CD8(-LYMPHOCYTE RESPONSE AND CONFERS A LEVEL OF PROTECTION COMPARABLE TO THAT OF WILD-TYPE HSV-1() CYTOTOXIC T)

Replication-deficient viruses provide an attractive alternative to con ventional approaches used in the induction of antiviral immunity. We h ave quantitatively evaluated both the primary and memory cytotoxic T-l ymphocyte (CTL) responses elicited by immunization with a replication- deficient mutant of herpes simplex virus type 1 (HSV-1). In addition, we have examined the potential role of these CTL in protection against HSV infection. Using bulk culture analysis and limiting-dilution anal ysis, we have shown that a replication-deficient virus, d301, generate s a strong primary CTL response that is comparable to the response ind uced by the wild type-strain, KOS1.1. Furthermore, the CTL induced by d301 immunization recognized the immunodominant, H-2K(b)-restricted, C TL recognition epitope gB398-505 to a level similar to that for CTL fr om KOS1.1-immunized mice. The memory CTL response evoked by d301 was s trong and persistent, even though the frequencies of CTL were slightly lower than the frequencies of CTL induced by KOS1.1. Adoptive transfe r studies indicated that both the CD8(+) and the CD4(+) T-cell respons es generated by immunization with d301 and KOS1.1 were able to limit t he extent of a cutaneous HSV infection to comparable levels. Overall, these results indicate that viral replication is not necessary to elic it a potent and durable HSV-specific immune response and suggest that replication-deficient viruses may be effective in eliciting protection against viral pathogens.