Modulation of Mucosal and Systemic Immunity by Enteric Administration of Nonreplicating Herpes Simplex Virus Expressing Cytokines

In this report the ability of enteric immunization with recombinant replication deficient (ICP4−/−) HSV expressing IFNγ to generate protection and modulate mucosal and systemic immunity was evaluated. ICP4−/−HSV, ICP4−/−HSV expressing IL4, live replicating, and uv HSV were used as controls. Following enteric administration of live HSV, a Th₁cytokine response was induced in the spleen, while both Th₁and notable Th₂cytokine production were detected at mucosal sites. Modulation of mucosal and systemic immune response was achieved when nonreplicating recombinant HSV viruses expressing cytokines were used. Compared to the control replication defective viruses, decreased frequency of Th₂cytokine producing cells in Peyer's patches was observed following enteric administration of nonreplicating HSV expressing IFNγ. When IFNγ expressing virus was given enterically, modulation was observed at the systemic level, measured by ELISPOT for cytokine producing cells, ELISA from thein vitrorestimulated splenic cell cultures, and by the increase of the IgG2a/IgG1 ratio in the serum. This report provides evidence that replication defective viruses expressing cytokine genes in contrast to uv HSV, are immunogenic when administered enterically and can generate significant immunomodulatory effects at the mucosal and systemic levels.