In this study we assessed prime-boost immunization strategies with a DNA va
ccine (gB DNA) and attenuated recombinant vaccinia virus vector (rvacgB), b
oth encoding the gB protein of HSV, for their effectiveness at inducing muc
osal as well as systemic immunity to HSV. Confirming the reports of others,
systemic priming with gB DNA and systemic boosting with rvacgB were the mo
st effective means of inducing serum Ab and splenic T cell responses. Never
theless, the systemic prime-boost approach failed to induce detectable Immo
ral or T cell responses at mucosal sites. However, such responses, at both
proximal and distal locations, were induced if immunizations, especially th
e priming dose, were administered mucosally. Curiously, whereas optimal imm
unity with systemic priming and boosting occurred when gB DNA was used to p
rime and rvacgB was used as a boost, mucosal responses were optimal when an
imals were mucosally primed with rvacgB and boosted with gB DNA given mucos
ally. Furthermore, notable mucosal responses also occurred in animals mucos
ally primed with rvacgB and subsequently boosted systemically with gB DNA.
Because the mucosal prime-boost immunization protocol also induced excellen
t systemic immune responses, the approach should be useful to vaccinate aga
inst agents for which both mucosal and systemic immunity are important for
protection.