HIV-1(89.6) Gag expressed from a replication competent HSV-1 vector elicits persistent cellular immune responses in mice.

We have constructed a replication competent, gamma(1)34.5-deleted herpes simplex virus type-1 (HSV-1) vector (J200) that expresses the gag gene from human immunodeficiency virus type-1, primary isolate 89.6 (HIV-1(89.6)), as a candidate vaccine for HIV-1. J200 replicates in vitro, resulting in abundant Gag protein production and accumulation in the extracellular media. Immunization of Balb/c mice with a single intraperitoneal injection of J200 elicited strong Gag-specific CD8 responses, as measured by intracellular IFN-gamma staining and flow cytometry analysis. Responses were highest between 6 weeks and 4 months, but persisted at 9 months post-immunization, the last time-point evaluated. These data highlight the potential utility of neuroattenuated, replication competent HSV-1 vectors for delivery of HIV-1 immunogens.