title: Successful topical respiratory tract immunization of primates against Ebola virus.
abstract: Ebola virus causes outbreaks of severe viral hemorrhagic fever with high mortality in humans. The virus is highly contagious and can be transmitted by contact and by the aerosol route. These features make Ebola virus a potential weapon for bioterrorism and biological warfare. Therefore, a vaccine that induces both systemic and local immune responses in the respiratory tract would be highly beneficial. We evaluated a common pediatric respiratory pathogen, human parainfluenza virus type 3 (HPIV3), as a vaccine vector against Ebola virus. HPIV3 recombinants expressing the Ebola virus (Zaire species) surface glycoprotein (GP) alone or in combination with the nucleocapsid protein NP or with the cytokine adjuvant granulocyte-macrophage colony-stimulating factor were administered by the respiratory route to rhesus monkeys--in which HPIV3 infection is mild and asymptomatic--and were evaluated for immunogenicity and protective efficacy against a highly lethal intraperitoneal challenge with Ebola virus. A single immunization with any construct expressing GP was moderately immunogenic against Ebola virus and protected 88% of the animals against severe hemorrhagic fever and death caused by Ebola virus. Two doses were highly immunogenic, and all of the animals survived challenge and were free of signs of disease and of detectable Ebola virus challenge virus. These data illustrate the feasibility of immunization via the respiratory tract against the hemorrhagic fever caused by Ebola virus. To our knowledge, this is the first study in which topical immunization through respiratory tract achieved prevention of a viral hemorrhagic fever infection in a primate model.
authors.affiliation: Laboratory of Infectious Disease, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-8007, USA. AB176v@nih.gov
authors.forename: Alexander
authors.initials: A
authors.lastname: Bukreyev
authors.forename: Pierre E
authors.initials: PE
authors.lastname: Rollin
authors.forename: Mallory K
authors.initials: MK
authors.lastname: Tate
authors.forename: Lijuan
authors.initials: L
authors.lastname: Yang
authors.forename: Sherif R
authors.initials: SR
authors.lastname: Zaki
authors.forename: Wun-Ju
authors.initials: WJ
authors.lastname: Shieh
authors.forename: Brian R
authors.initials: BR
authors.lastname: Murphy
authors.forename: Peter L
authors.initials: PL
authors.lastname: Collins
authors.forename: Anthony
authors.initials: A
authors.lastname: Sanchez
mesh_terms: D000818:Animals; D046129:Ebola Vaccines / Q000737:chemistry* / Q000627:therapeutic use*; D029043:Ebolavirus / Q000276:immunology*; D005822:Genetic Vectors; D019142:Hemorrhagic Fever, Ebola / Q000517:prevention & control*; D007114:Immunization; D008253:Macaca mulatta; D010224:Parainfluenza Virus 3, Human / Q000235:genetics; D012137:Respiratory System / Q000821:virology*; D012140:Respiratory Tract Diseases / Q000517:prevention & control*; D016896:Treatment Outcome; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000378:metabolism; D014779:Virus Replication
chemical_list: D046129:Ebola Vaccines; D014759:Viral Envelope Proteins; C113189:envelope glycoprotein, Ebola virus