title: Genetically engineered herpes simplex viruses that express IL-12 or GM-CSF as vaccine candidates.
abstract: We are using genetically modified, conditionally replicating herpes simplex virus (HSV) that express either interleukin (IL)-12 or granulocyte macrophage-colony stimulating factor (GM-CSF) as live, attenuated vaccine candidates for protection against HSV infection and/or disease. We report the following: (1) animals previously vaccinated with these candidate vaccines exhibited dose-dependent protection after intranasal, intraperitoneal or intracranial challenge with the highly virulent E377-MB wild-type HSV-1; (2) the IL-12 expressing virus (M002) consistently conferred protection at lower immunization doses than GM-CSF expressing virus (M004); (3) between 80 and 100% protection from E377-MB challenge was conferred after intramuscular immunization of mice with any of the three Deltagamma1 34.5 HSV, as opposed to 50% protection elicited after immunization with wild-type HSV-1 (F); and (4) latent virus was not detected at a higher rate in animals immunized and subsequently challenged with E377-MB than in immunized animals alone. These data suggest that conditionally replicating, cytokine-expressing HSV are able to elicit protective immune responses while retaining safety in an experimental murine model.
authors.affiliation: Department of Pediatrics, Division of Infectious Diseases, The University of Alabama at Birmingham, CHB 118B, 1600 6th Avenue South, Birmingham, AL 35233, USA. jnparker@uab.edu
authors.forename: Jacqueline N
authors.initials: JN
authors.lastname: Parker
authors.forename: Luz-Andrea
authors.initials: LA
authors.lastname: Pfister
authors.forename: Debra
authors.initials: D
authors.lastname: Quenelle
authors.forename: G Yancey
authors.initials: GY
authors.lastname: Gillespie
authors.forename: James M
authors.initials: JM
authors.lastname: Markert
authors.forename: Earl R
authors.initials: ER
authors.lastname: Kern
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Whitley
mesh_terms: D000818:Animals; D005260:Female; D005818:Genetic Engineering; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics*; D022301:Herpes Simplex Virus Vaccines / Q000008:administration & dosage / Q000276:immunology*; D018664:Interleukin-12 / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D018139:Simplexvirus / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology; D012668:Trigeminal Ganglion / Q000821:virology; D014613:Vaccines, Attenuated / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology*; D014774:Virulence; D014775:Virus Activation; D014779:Virus Replication
chemical_list: D022301:Herpes Simplex Virus Vaccines; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; D018664:Interleukin-12; D016178:Granulocyte-Macrophage Colony-Stimulating Factor