title: De novo syntheses of Marburg virus antigens from adenovirus vectors induce potent humoral and cellular immune responses.
abstract: Marburg virus (MARV) is an African filovirus that causes a deadly hemorrhagic fever in humans, with up to 90% mortality. Currently, there are no MARV vaccines or therapies approved for human use. We hypothesized that developing a vaccine that induces a de novo synthesis of MARV antigens in vivo will lead to strong induction of both a humoral and cell-mediated immune response against MARV. Here, we develop and characterize three novel gene-based vaccine candidates which express the viral glycoprotein (GP) from either the Ci67, Ravn or Musoke strain of MARV. Immunization of mice with complex adenovirus (Ad)-based vaccine candidates (cAdVax vaccines), led to efficient production of both antibodies and cytotoxic T lymphocytes (CTL) specific to Musoke strain GP and Ci67 strain GP, respectively. Antibody responses were also shown to be cross-reactive across the MARV strains, but not cross-reactive to Ebola virus, a related filovirus. Additionally, three 1 x 10(8)pfu doses of vaccine vector were demonstrated to be safe in mice, as this did not lead to any detectable toxicity in liver or spleen. These promising results indicate that a cAdVax-based vaccine could be effective for induction of both humoral and cell-mediated immune responses to multiple strains of the Marburg virus.
authors.affiliation: Division of Biodefense Vaccines, GenPhar Inc., 871 Lowcountry Blvd., Mount Pleasant, SC 29464, USA.
authors.forename: Danher
authors.initials: D
authors.lastname: Wang
authors.forename: Alan L
authors.initials: AL
authors.lastname: Schmaljohn
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: Stephen B
authors.initials: SB
authors.lastname: Deitz
authors.forename: Hong
authors.initials: H
authors.lastname: Yu
authors.forename: Jan
authors.initials: J
authors.lastname: Woraratanadharm
authors.forename: David H
authors.initials: DH
authors.lastname: Holman
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Moore
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Swain
authors.forename: William D
authors.initials: WD
authors.lastname: Pratt
authors.forename: John Y
authors.initials: JY
authors.lastname: Dong
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D003429:Cross Reactions; D003601:Cytotoxicity Tests, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D005822:Genetic Vectors; D006801:Humans; D008099:Liver / Q000473:pathology; D008379:Marburg Virus Disease / Q000276:immunology / Q000517:prevention & control*; D029024:Marburgvirus / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D013154:Spleen / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014759:Viral Envelope Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; C081324:GP-protein, Marburg virus; D014759:Viral Envelope Proteins; D014765:Viral Vaccines