title: Immunization with herpes simplex virus 2 (HSV-2) genes plus inactivated HSV-2 is highly protective against acute and recurrent HSV-2 disease.
abstract: To date, no vaccine that is safe and effective against herpes simplex virus 2 (HSV-2) disease has been licensed. In this study, we evaluated a DNA prime-formalin-inactivated-HSV-2 (FI-HSV2) boost vaccine approach in the guinea pig model of acute and recurrent HSV-2 genital disease. Five groups of guinea pigs were immunized and intravaginally challenged with HSV-2. Two groups were primed with plasmid DNAs encoding the secreted form of glycoprotein D2 (gD2t) together with two genes required for viral replication, either the helicase (UL5) and DNA polymerase (UL30) genes or the single-stranded DNA binding protein (UL29) and primase (UL52) genes. Both DNA-primed groups were boosted with FI-HSV2 formulated with monophosphoryl lipid A (MPL) and alum adjuvants. Two additional groups were primed with the empty backbone plasmid DNA (pVAX). These two groups were boosted with MPL and alum (MPL-alum) together with either formalin-inactivated mock HSV-2 (FI-Mock) or with FI-HSV2. The final group was immunized with gD2t protein in MPL-alum. After challenge, 0/9 animals in the group primed with UL5, UL30, and gD2t DNAs and all 10 animals in the mock-immunized control group (pVAX-FI-Mock) developed primary lesions. All mock controls developed recurrent lesions through day 100 postchallenge. Only 1 guinea pig in the group primed with pVAX DNA and boosted with FI-HSV2 (pVAX-FI-HSV2 group) and 2 guinea pigs in the group primed with UL5, UL30, and gD2t DNAs and boosted with FI-HSV2 (UL5, UL30, gD2t DNA-FI-HSV2 group) developed recurrent lesions. Strikingly, the UL5, UL30, gD2t DNA-FI-HSV2 group showed a 97% reduction in recurrent lesion days compared with the mock controls, had the highest reduction in days with recurrent disease, and contained the lowest mean HSV-2 DNA load in the dorsal root ganglia.
authors.affiliation: Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Dr., 0712, La Jolla, CA 92093-0712, USA.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Morello
authors.forename: Michael S
authors.initials: MS
authors.lastname: Levinson
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Kraynyak
authors.forename: Deborah H
authors.initials: DH
authors.lastname: Spector
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000534:Alum Compounds / Q000008:administration & dosage; D000818:Animals; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D005727:Ganglia, Spinal / Q000821:virology; D006168:Guinea Pigs; D006558:Herpes Genitalis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D018258:Herpesvirus 2, Human / Q000235:genetics / Q000276:immunology*; D022283:Herpesvirus Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007117:Immunization, Secondary / Q000379:methods*; D008050:Lipid A / Q000008:administration & dosage / Q000031:analogs & derivatives; D055502:Secondary Prevention; D014611:Vaccination / Q000379:methods*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D004279:DNA, Viral; D022283:Herpesvirus Vaccines; D008050:Lipid A; D019444:Vaccines, DNA; D015164:Vaccines, Inactivated; C041524:aluminum sulfate; C048436:monophosphoryl lipid A