title: A Single Dose Respiratory Recombinant Adenovirus-Based Vaccine Provides Long-Term Protection for Non-Human Primates from Lethal Ebola Infection.
abstract: As the Ebola outbreak in West Africa continues and cases appear in the United States and other countries, the need for long-lasting vaccines to preserve global health is imminent. Here, we evaluate the long-term efficacy of a respiratory and sublingual (SL) adenovirus-based vaccine in non-human primates in two phases. In the first, a single respiratory dose of 1.4×10(9) infectious virus particles (ivp)/kg of Ad-CAGoptZGP induced strong Ebola glycoprotein (GP) specific CD8+ and CD4+ T cell responses and Ebola GP-specific antibodies in systemic and mucosal compartments and was partially (67%) protective from challenge 62 days after immunization. The same dose given by the SL route induced Ebola GP-specific CD8+ T cell responses similar to that of intramuscular (IM) injection, however, the Ebola GP-specific antibody response was low. All primates succumbed to infection. Three primates were then given the vaccine in a formulation that improved the immune response to Ebola in rodents. Three primates were immunized with 2.0×10(10) ivp/kg of vaccine by the SL route. Diverse populations of polyfunctional Ebola GP-specific CD4+ and CD8+ T cells and significant anti-Ebola GP antibodies were present in samples collected 150 days after respiratory immunization. The formulated vaccine was fully protective against challenge 21 weeks after immunization. While diverse populations of Ebola GP-specific CD4+ T cells were produced after SL immunization, antibodies were not neutralizing and the vaccine was unprotective. To our knowledge, this is the first time that durable protection from a single dose respiratory adenovirus-based Ebola vaccine has been demonstrated in primates.
authors.affiliation: †Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, Austin, Texas 78712, United States.
authors.forename: Jin Huk
authors.initials: JH
authors.lastname: Choi
authors.affiliation: †Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, Austin, Texas 78712, United States.
authors.forename: Kristina
authors.initials: K
authors.lastname: Jonsson-Schmunk
authors.affiliation: §Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada.
authors.forename: Xiangguo
authors.initials: X
authors.lastname: Qiu
authors.affiliation: ∥Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.
authors.forename: Devon J
authors.initials: DJ
authors.lastname: Shedlock
authors.affiliation: §Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada.
authors.forename: Jim
authors.initials: J
authors.lastname: Strong
authors.affiliation: †Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, Austin, Texas 78712, United States.
authors.forename: Jason X
authors.initials: JX
authors.lastname: Xu
authors.affiliation: ⊥The University of Texas College of Natural Sciences Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, Texas 78712, United States.
authors.forename: Kelly L
authors.initials: KL
authors.lastname: Michie
authors.affiliation: §Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Audet
authors.affiliation: §Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada.
authors.forename: Lisa
authors.initials: L
authors.lastname: Fernando
authors.affiliation: †Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, Austin, Texas 78712, United States.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Myers
authors.affiliation: ∥Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.
authors.forename: David
authors.initials: D
authors.lastname: Weiner
authors.affiliation: #Department of Biochemistry, College of Natural Sciences, The University of Texas at Austin, Austin, Texas 78712, United States.
authors.forename: Irnela
authors.initials: I
authors.lastname: Bajrovic
authors.affiliation: †Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, Austin, Texas 78712, United States.
authors.forename: Lilian Q
authors.initials: LQ
authors.lastname: Tran
authors.affiliation: §Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada.
authors.forename: Gary
authors.initials: G
authors.lastname: Wong
authors.affiliation: §Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada.
authors.forename: Alexander
authors.initials: A
authors.lastname: Bello
authors.affiliation: §Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada.|∥Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.
authors.forename: Gary P
authors.initials: GP
authors.lastname: Kobinger
authors.affiliation: †Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, Austin, Texas 78712, United States.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Schafer
authors.affiliation: †Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, Austin, Texas 78712, United States.|⊥The University of Texas College of Natural Sciences Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, Texas 78712, United States.|¶Center for Infectious Disease, The University of Texas at Austin, Austin, Texas 78712, United States.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Croyle
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000276:immunology*; D000818:Animals; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D046129:Ebola Vaccines / Q000008:administration & dosage*; D029043:Ebolavirus / Q000276:immunology*; D057809:HEK293 Cells; D019142:Hemorrhagic Fever, Ebola / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D008252:Macaca fascicularis; D008297:Male; D014611:Vaccination / Q000379:methods; D014614:Vaccines, Synthetic / Q000008:administration & dosage* / Q000235:genetics; D014709:Vero Cells
chemical_list: D046129:Ebola Vaccines; D014614:Vaccines, Synthetic
keywords: Ebola; adenovirus; non-human primate; respiratory; sublingual; vaccine