title: CD8+ cellular immunity mediates rAd5 vaccine protection against Ebola virus infection of nonhuman primates.
abstract: Vaccine-induced immunity to Ebola virus infection in nonhuman primates (NHPs) is marked by potent antigen-specific cellular and humoral immune responses; however, the immune mechanism of protection remains unknown. Here we define the immune basis of protection conferred by a highly protective recombinant adenovirus virus serotype 5 (rAd5) encoding Ebola virus glycoprotein (GP) in NHPs. Passive transfer of high-titer polyclonal antibodies from vaccinated Ebola virus-immune cynomolgus macaques to naive macaques failed to confer protection against disease, suggesting a limited role of humoral immunity. In contrast, depletion of CD3(+) T cells in vivo after vaccination and immediately before challenge eliminated immunity in two vaccinated macaques, indicating a crucial requirement for T cells in this setting. The protective effect was mediated largely by CD8(+) cells, as depletion of CD8(+) cells in vivo using the cM-T807 monoclonal antibody (mAb), which does not affect CD4(+) T cell or humoral immune responses, abrogated protection in four out of five subjects. These findings indicate that CD8(+) cells have a major role in rAd5-GP-induced immune protection against Ebola virus infection in NHPs. Understanding the immunologic mechanism of Ebola virus protection will facilitate the development of vaccines for Ebola and related hemorrhagic fever viruses in humans.
authors.affiliation: Vaccine Research Center, US National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Bethesda, Maryland, USA. nsullivan@nih.gov
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Sullivan
authors.forename: Lisa
authors.initials: L
authors.lastname: Hensley
authors.forename: Clement
authors.initials: C
authors.lastname: Asiedu
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Geisbert
authors.forename: Daphne
authors.initials: D
authors.lastname: Stanley
authors.forename: Joshua
authors.initials: J
authors.lastname: Johnson
authors.forename: Anna
authors.initials: A
authors.lastname: Honko
authors.forename: Gene
authors.initials: G
authors.lastname: Olinger
authors.forename: Michael
authors.initials: M
authors.lastname: Bailey
authors.forename: Joan B
authors.initials: JB
authors.lastname: Geisbert
authors.forename: Keith A
authors.initials: KA
authors.lastname: Reimann
authors.forename: Saran
authors.initials: S
authors.lastname: Bao
authors.forename: Srinivas
authors.initials: S
authors.lastname: Rao
authors.forename: Mario
authors.initials: M
authors.lastname: Roederer
authors.forename: Peter B
authors.initials: PB
authors.lastname: Jahrling
authors.forename: Richard A
authors.initials: RA
authors.lastname: Koup
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Nabel
mesh_terms: D000256:Adenoviridae / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D046129:Ebola Vaccines / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019142:Hemorrhagic Fever, Ebola / Q000276:immunology* / Q000517:prevention & control*; D007150:Immunohistochemistry; D008252:Macaca fascicularis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014759:Viral Envelope Proteins / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D017252:CD3 Complex; D046129:Ebola Vaccines; D014759:Viral Envelope Proteins