title: Immunization with a vaccinia virus recombinant expressing herpes simplex virus type 1 glycoprotein D: long-term protection and effect of revaccination.
abstract: 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.
authors.affiliation: Laboratory of Oral Medicine, National Institute of Dental Research, Bethesda, Maryland 20892.
authors.forename: J F
authors.initials: JF
authors.lastname: Rooney
authors.forename: C
authors.initials: C
authors.lastname: Wohlenberg
authors.forename: K J
authors.initials: KJ
authors.lastname: Cremer
authors.forename: B
authors.initials: B
authors.lastname: Moss
authors.forename: A L
authors.initials: AL
authors.lastname: Notkins
mesh_terms: D000818:Animals; D005260:Female; D006561:Herpes Simplex / Q000517:prevention & control; D007114:Immunization; D007117:Immunization, Secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D011995:Recombination, Genetic; D018139:Simplexvirus / Q000276:immunology*; D013997:Time Factors; D012668:Trigeminal Ganglion / Q000382:microbiology; D014616:Vaccinia virus / Q000235:genetics*; D014759:Viral Envelope Proteins / Q000235:genetics*
chemical_list: D014759:Viral Envelope Proteins; C039447:glycoprotein D, Human herpesvirus 1