title: Inactivated or live-attenuated bivalent vaccines that confer protection against rabies and Ebola viruses.
abstract: The search for a safe and efficacious vaccine for Ebola virus continues, as no current vaccine candidate is nearing licensure. We have developed (i) replication-competent, (ii) replication-deficient, and (iii) chemically inactivated rabies virus (RABV) vaccines expressing Zaire Ebola virus (ZEBOV) glycoprotein (GP) by a reverse genetics system based on the SAD B19 RABV wildlife vaccine. ZEBOV GP is efficiently expressed by these vaccine candidates and is incorporated into virions. The vaccine candidates were avirulent after inoculation of adult mice, and viruses with a deletion in the RABV glycoprotein had greatly reduced neurovirulence after intracerebral inoculation in suckling mice. Immunization with live or inactivated RABV vaccines expressing ZEBOV GP induced humoral immunity against each virus and conferred protection from both lethal RABV and EBOV challenge in mice. The bivalent RABV/ZEBOV vaccines described here have several distinct advantages that may speed the development of inactivated vaccines for use in humans and potentially live or inactivated vaccines for use in nonhuman primates at risk of EBOV infection in endemic areas.
authors.affiliation: Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. jblaney@niaid.nih.gov
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Blaney
authors.forename: Christoph
authors.initials: C
authors.lastname: Wirblich
authors.forename: Amy B
authors.initials: AB
authors.lastname: Papaneri
authors.forename: Reed F
authors.initials: RF
authors.lastname: Johnson
authors.forename: Carey J
authors.initials: CJ
authors.lastname: Myers
authors.forename: Terry L
authors.initials: TL
authors.lastname: Juelich
authors.forename: Michael R
authors.initials: MR
authors.lastname: Holbrook
authors.forename: Alexander N
authors.initials: AN
authors.lastname: Freiberg
authors.forename: John G
authors.initials: JG
authors.lastname: Bernbaum
authors.forename: Peter B
authors.initials: PB
authors.lastname: Jahrling
authors.forename: Jason
authors.initials: J
authors.lastname: Paragas
authors.forename: Matthias J
authors.initials: MJ
authors.lastname: Schnell
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001921:Brain / Q000821:virology; D004195:Disease Models, Animal; D046129:Ebola Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology*; D029043:Ebolavirus / Q000235:genetics / Q000276:immunology; D019142:Hemorrhagic Fever, Ebola / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D011818:Rabies / Q000517:prevention & control; D011819:Rabies Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology*; D011820:Rabies virus / Q000235:genetics / Q000276:immunology; D012376:Rodent Diseases / Q000517:prevention & control; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology; D014774:Virulence
chemical_list: D000914:Antibodies, Viral; D046129:Ebola Vaccines; D011819:Rabies Vaccines; D014613:Vaccines, Attenuated; D015164:Vaccines, Inactivated; D014614:Vaccines, Synthetic