Previously we showed that mice immunized with a vaccinia virus vector expressing the herpes simplex virus type 1 (HSV-1)
glycoprotein D (gD) gene (
vaccinia/gD) were protected against both lethal and
latent infections with HSV-1 for at least 6 weeks after immunization (K. J. Cremer, M. Mackett, C. Wohlenberg, A. L. Notkins, and B. Moss, Science 228:737-740, 1985). In the experiments described here, we examined long-term immunity to HSV following
vaccinia/gD vaccination, the effect of revaccination with
vaccinia/gD, and the impact of previous immunity to vaccinia virus on immunization with the gD recombinant. Mice immunized with
vaccinia/gD showed 100, 100, and 80% protection against lethal
infection with HSV-1 at 18, 44, and 60 weeks postimmunization, respectively. Protection against latent trigeminal ganglionic
infection was 70, 50, and 31% at 6, 41, and 60 weeks postvaccination, respectively. To study the effect of reimmunization on antibody levels, mice vaccinated with
vaccinia/gD were given a second immunization (booster dose) 3 months after the first. These mice developed a 10-fold increase in
neutralizing-antibody titer (221 to 2,934) and demonstrated a significant increase in protection against lethal HSV-1 challenge compared with animals that received only one dose of
vaccinia/gD. To determine whether preexisting immunity to vaccinia virus inhibited the response to vaccination with
vaccinia/gD virus, mice were immunized with a recombinant vaccinia virus vector expressing
antigens from either
influenza A or hepatitis B virus and were then immunized (2 to 3 months later) with
vaccinia/gD. These mice showed reduced titers of
neutralizing antibody to HSV-1 and decreased protection against both lethal and
latent infections with HSV-1 compared with animals vaccinated only with
vaccinia/gD. We conclude that vaccination with
vaccinia/gD produces immunity against HSV-1 that lasts over 1 year and that this immunity can be increased by a booster but that prior immunization with a
vaccinia recombinant virus expressing a non-HSV gene reduces the levels of
neutralizing antibody and protective immunity against HSV-1 challenge.