title: Recombinant adenovirus serotype 26 (Ad26) and Ad35 vaccine vectors bypass immunity to Ad5 and protect nonhuman primates against ebolavirus challenge.
abstract: The use of adenoviruses (Ad) as vaccine vectors against a variety of pathogens has demonstrated their capacity to elicit strong antibody and cell-mediated immune responses. Adenovirus serotype C vectors, such as Ad serotype 5 (Ad5), expressing Ebolavirus (EBOV) glycoprotein (GP), protect completely after a single inoculation at a dose of 10(10) viral particles. However, the clinical application of a vaccine based on Ad5 vectors may be hampered, since impairment of Ad5 vaccine efficacy has been demonstrated for humans and nonhuman primates with high levels of preexisting immunity to the vector. Ad26 and Ad35 segregate genetically from Ad5 and exhibit lower seroprevalence in humans, making them attractive vaccine vector alternatives. In the series of studies presented, we show that Ad26 and Ad35 vectors generate robust antigen-specific cell-mediated and humoral immune responses against EBOV GP and that Ad5 immune status does not affect the generation of GP-specific immune responses by these vaccines. We demonstrate partial protection against EBOV by a single-shot Ad26 vaccine and complete protection when this vaccine is boosted by Ad35 1 month later. Increases in efficacy are paralleled by substantial increases in T- and B-cell responses to EBOV GP. These results suggest that Ad26 and Ad35 vectors warrant further development as candidate vaccines for EBOV.
authors.affiliation: United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland 21702-5011, USA.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Geisbert
authors.forename: Michael
authors.initials: M
authors.lastname: Bailey
authors.forename: Lisa
authors.initials: L
authors.lastname: Hensley
authors.forename: Clement
authors.initials: C
authors.lastname: Asiedu
authors.forename: Joan
authors.initials: J
authors.lastname: Geisbert
authors.forename: Daphne
authors.initials: D
authors.lastname: Stanley
authors.forename: Anna
authors.initials: A
authors.lastname: Honko
authors.forename: Joshua
authors.initials: J
authors.lastname: Johnson
authors.forename: Sabue
authors.initials: S
authors.lastname: Mulangu
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Pau
authors.forename: Jerome
authors.initials: J
authors.lastname: Custers
authors.forename: Jort
authors.initials: J
authors.lastname: Vellinga
authors.forename: Jenny
authors.initials: J
authors.lastname: Hendriks
authors.forename: Peter
authors.initials: P
authors.lastname: Jahrling
authors.forename: Mario
authors.initials: M
authors.lastname: Roederer
authors.forename: Jaap
authors.initials: J
authors.lastname: Goudsmit
authors.forename: Richard
authors.initials: R
authors.lastname: Koup
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Sullivan
mesh_terms: D000260:Adenoviruses, Human / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D004337:Drug Carriers; D046129:Ebola Vaccines / Q000008:administration & dosage / Q000276:immunology*; D005822:Genetic Vectors / Q000276:immunology*; D019142:Hemorrhagic Fever, Ebola / Q000276:immunology / Q000517:prevention & control*; D008214:Lymphocytes / Q000276:immunology; D008252:Macaca fascicularis; D014611:Vaccination / Q000379:methods; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D004337:Drug Carriers; D046129:Ebola Vaccines; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; C113189:envelope glycoprotein, Ebola virus