title: Development of a cAdVax-based bivalent ebola virus vaccine that induces immune responses against both the Sudan and Zaire species of Ebola virus.
abstract: Ebola virus (EBOV) causes a severe hemorrhagic fever for which there are currently no vaccines or effective treatments. While lethal human outbreaks have so far been restricted to sub-Saharan Africa, the potential exploitation of EBOV as a biological weapon cannot be ignored. Two species of EBOV, Sudan ebolavirus (SEBOV) and Zaire ebolavirus (ZEBOV), have been responsible for all of the deadly human outbreaks resulting from this virus. Therefore, it is important to develop a vaccine that can prevent infection by both lethal species. Here, we describe the bivalent cAdVaxE(GPs/z) vaccine, which includes the SEBOV glycoprotein (GP) and ZEBOV GP genes together in a single complex adenovirus-based vaccine (cAdVax) vector. Vaccination of mice with the bivalent cAdVaxE(GPs/z) vaccine led to efficient induction of EBOV-specific antibody and cell-mediated immune responses to both species of EBOV. In addition, the cAdVax technology demonstrated induction of a 100% protective immune response in mice, as all vaccinated C57BL/6 and BALB/c mice survived challenge with a lethal dose of ZEBOV (30,000 times the 50% lethal dose). This study demonstrates the potential efficacy of a bivalent EBOV vaccine based on a cAdVax vaccine vector design.
authors.affiliation: Division of Biodefense Vaccines, GenPhar, Inc., 871 Lowcountry Blvd., Mount Pleasant, South Carolina 29464, USA.
authors.forename: Danher
authors.initials: D
authors.lastname: Wang
authors.forename: Nicholas U
authors.initials: NU
authors.lastname: Raja
authors.forename: Charles M
authors.initials: CM
authors.lastname: Trubey
authors.forename: Laure Y
authors.initials: LY
authors.lastname: Juompan
authors.forename: Min
authors.initials: M
authors.lastname: Luo
authors.forename: Jan
authors.initials: J
authors.lastname: Woraratanadharm
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Deitz
authors.forename: Hong
authors.initials: H
authors.lastname: Yu
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Swain
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Moore
authors.forename: William D
authors.initials: WD
authors.lastname: Pratt
authors.forename: Mary Kate
authors.initials: MK
authors.lastname: Hart
authors.forename: John Y
authors.initials: JY
authors.lastname: Dong
mesh_terms: D000256:Adenoviridae / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002460:Cell Line; D046129:Ebola Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D029043:Ebolavirus / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity; D006367:HeLa Cells; D019142:Hemorrhagic Fever, Ebola / Q000276:immunology* / Q000517:prevention & control* / Q000821:virology; D006801:Humans; D007111:Immunity, Cellular; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013045:Species Specificity; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D000914:Antibodies, Viral; D046129:Ebola Vaccines; D014759:Viral Envelope Proteins; C113189:envelope glycoprotein, Ebola virus