title: Ad35 and ad26 vaccine vectors induce potent and cross-reactive antibody and T-cell responses to multiple filovirus species.
abstract: Filoviruses cause sporadic but highly lethal outbreaks of hemorrhagic fever in Africa in the human population. Currently, no drug or vaccine is available for treatment or prevention. A previous study with a vaccine candidate based on the low seroprevalent adenoviruses 26 and 35 (Ad26 and Ad35) was shown to provide protection against homologous Ebola Zaire challenge in non human primates (NHP) if applied in a prime-boost regimen. Here we have aimed to expand this principle to construct and evaluate Ad26 and Ad35 vectors for development of a vaccine to provide universal filovirus protection against all highly lethal strains that have caused major outbreaks in the past. We have therefore performed a phylogenetic analysis of filovirus glycoproteins to select the glycoproteins from two Ebola species (Ebola Zaire and Ebola Sudan/Gulu,), two Marburg strains (Marburg Angola and Marburg Ravn) and added the more distant non-lethal Ebola Ivory Coast species for broadest coverage. Ad26 and Ad35 vectors expressing these five filovirus glycoproteins were evaluated to induce a potent cellular and humoral immune response in mice. All adenoviral vectors induced a humoral immune response after single vaccination in a dose dependent manner that was cross-reactive within the Ebola and Marburg lineages. In addition, both strain-specific as well as cross-reactive T cell responses could be detected. A heterologous Ad26-Ad35 prime-boost regime enhanced mainly the humoral and to a lower extend the cellular immune response against the transgene. Combination of the five selected filovirus glycoproteins in one multivalent vaccine potentially elicits protective immunity in man against all major filovirus strains that have caused lethal outbreaks in the last 20 years.
authors.affiliation: Crucell Holland BV, Leiden, The Netherlands.
authors.forename: Roland
authors.initials: R
authors.lastname: Zahn
authors.forename: Gert
authors.initials: G
authors.lastname: Gillisen
authors.forename: Anna
authors.initials: A
authors.lastname: Roos
authors.forename: Marina
authors.initials: M
authors.lastname: Koning
authors.forename: Esmeralda
authors.initials: E
authors.lastname: van der Helm
authors.forename: Dirk
authors.initials: D
authors.lastname: Spek
authors.forename: Mo
authors.initials: M
authors.lastname: Weijtens
authors.forename: Maria
authors.initials: M
authors.lastname: Grazia Pau
authors.forename: Katarina
authors.initials: K
authors.lastname: Radošević
authors.forename: Gerrit Jan
authors.initials: GJ
authors.lastname: Weverling
authors.forename: Jerome
authors.initials: J
authors.lastname: Custers
authors.forename: Jort
authors.initials: J
authors.lastname: Vellinga
authors.forename: Hanneke
authors.initials: H
authors.lastname: Schuitemaker
authors.forename: Jaap
authors.initials: J
authors.lastname: Goudsmit
authors.forename: Ariane
authors.initials: A
authors.lastname: Rodríguez
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000276:immunology; D000818:Animals; D000914:Antibodies, Viral / Q000235:genetics / Q000276:immunology; D003429:Cross Reactions; D046129:Ebola Vaccines / Q000235:genetics / Q000276:immunology*; D005260:Female; D016563:Filoviridae / Q000276:immunology*; D005822:Genetic Vectors; D019142:Hemorrhagic Fever, Ebola / Q000276:immunology / Q000517:prevention & control*; D056724:Immunity, Humoral / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000276:immunology*; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D046129:Ebola Vaccines; D014765:Viral Vaccines