The impact of vaccination with plasmid DNA encoding full-length glycoprotei
n D (gD) from herpes simplex virus (HSV) type 2 (gD2), secreted gD2, or cyt
osolic gD2 was evaluated in mice and guinea pigs. Immunization with plasmid
s encoding full-length gD2 or secreted gD2 produced high antibody levels, w
hereas immunization with DNA encoding cytosolic gD2 resulted in significant
ly lower antibody titers in both species (P < .001). Vaccination with DNA e
ncoding full-length or secreted gD2 significantly reduced acute disease in
mice and guinea pigs (both P < .001) and subsequent recurrent disease in gu
inea pigs (P < .05). In guinea pigs, immunization with DNA encoding cytosol
ic gD2 did not protect from acute or recurrent disease, whereas in mice it
did protect, but not as well as DNA encoding full-length or secreted gD2. N
one of the vaccines resulted in improved virus clearance from the inoculati
on site, and none significantly reduced recurrent disease when used as a th
erapeutic vaccine in HSV-2-infected guinea pigs.