Systemic and mucosal antibody responses following retroductal gene transfer to the salivary gland.

Gene transfer to salivary glands by retrograde perfusion of the salivary duct has been shown to result in production of the encoded protein. We sought to determine if this technique would be useful for genetic immunization. In studies that compare delivery of DNA to either the salivary gland (SG) or muscle (im), mean plasma IgG and IgA titers obtained following SG delivery were 46- and 86-fold greater, respectively, than those following im delivery. We also tested the hypothesis that SG vaccination could generate mucosal responses in sites proximal and distal to DNA administration. SG-treated animals produced specific antibodies within saliva, vaginal fluid, and lung washes as well as demonstrating robust specific responses in Peyer's patches. In a test of functional immunity, animals vaccinated with DNA by SG retrograde perfusion were significantly more resistant to the effects of lethal anthrax challenge than im DNA-vaccinated animals. These data suggest that SG genetic immunization may offer advantages over conventional routes of vaccination.