title: Protective monotherapy against lethal Ebola virus infection by a potently neutralizing antibody.
abstract: Ebola virus disease in humans is highly lethal, with case fatality rates ranging from 25 to 90%. There is no licensed treatment or vaccine against the virus, underscoring the need for efficacious countermeasures. We ascertained that a human survivor of the 1995 Kikwit Ebola virus disease outbreak maintained circulating antibodies against the Ebola virus surface glycoprotein for more than a decade after infection. From this survivor we isolated monoclonal antibodies (mAbs) that neutralize recent and previous outbreak variants of Ebola virus and mediate antibody-dependent cell-mediated cytotoxicity in vitro. Strikingly, monotherapy with mAb114 protected macaques when given as late as 5 days after challenge. Treatment with a single human mAb suggests that a simplified therapeutic strategy for human Ebola infection may be possible.
authors.affiliation: Institute for Research in Biomedicine, Università della Svizzera Italiana, CH-6500 Bellinzona, Switzerland. Humabs BioMed SA, 6500 Bellinzona, Switzerland.
authors.forename: Davide
authors.initials: D
authors.lastname: Corti
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
authors.forename: John
authors.initials: J
authors.lastname: Misasi
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
authors.forename: Sabue
authors.initials: S
authors.lastname: Mulangu
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
authors.forename: Daphne A
authors.initials: DA
authors.lastname: Stanley
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
authors.forename: Masaru
authors.initials: M
authors.lastname: Kanekiyo
authors.affiliation: U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Wollen
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Ploquin
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Doria-Rose
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
authors.forename: Ryan P
authors.initials: RP
authors.lastname: Staupe
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Bailey
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
authors.forename: Misook
authors.initials: M
authors.lastname: Choe
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
authors.forename: Hadar
authors.initials: H
authors.lastname: Marcus
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
authors.forename: Emily A
authors.initials: EA
authors.lastname: Thompson
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
authors.forename: Alberto
authors.initials: A
authors.lastname: Cagigi
authors.affiliation: Institute for Research in Biomedicine, Università della Svizzera Italiana, CH-6500 Bellinzona, Switzerland.
authors.forename: Chiara
authors.initials: C
authors.lastname: Silacci
authors.affiliation: Institute for Research in Biomedicine, Università della Svizzera Italiana, CH-6500 Bellinzona, Switzerland.
authors.forename: Blanca
authors.initials: B
authors.lastname: Fernandez-Rodriguez
authors.affiliation: Institute for Research in Biomedicine, Università della Svizzera Italiana, CH-6500 Bellinzona, Switzerland.
authors.forename: Laurent
authors.initials: L
authors.lastname: Perez
authors.affiliation: Institute for Research in Biomedicine, Università della Svizzera Italiana, CH-6500 Bellinzona, Switzerland.
authors.forename: Federica
authors.initials: F
authors.lastname: Sallusto
authors.affiliation: Humabs BioMed SA, 6500 Bellinzona, Switzerland.
authors.forename: Fabrizia
authors.initials: F
authors.lastname: Vanzetta
authors.affiliation: Humabs BioMed SA, 6500 Bellinzona, Switzerland.
authors.forename: Gloria
authors.initials: G
authors.lastname: Agatic
authors.affiliation: Humabs BioMed SA, 6500 Bellinzona, Switzerland.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Cameroni
authors.affiliation: National Institute for Biomedical Research, National Laboratory of Public Health, Kinshasa B.P. 1197, Democratic Republic of the Congo.
authors.forename: Neville
authors.initials: N
authors.lastname: Kisalu
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
authors.forename: Ingelise
authors.initials: I
authors.lastname: Gordon
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
authors.forename: Julie E
authors.initials: JE
authors.lastname: Ledgerwood
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Mascola
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
authors.forename: Barney S
authors.initials: BS
authors.lastname: Graham
authors.affiliation: National Institute for Biomedical Research, National Laboratory of Public Health, Kinshasa B.P. 1197, Democratic Republic of the Congo.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Muyembe-Tamfun
authors.affiliation: U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Trefry
authors.affiliation: Institute for Research in Biomedicine, Università della Svizzera Italiana, CH-6500 Bellinzona, Switzerland. Institute of Microbiology, ETH Zürich, CH-8093 Zürich, Switzerland.
authors.forename: Antonio
authors.initials: A
authors.lastname: Lanzavecchia
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA. njsull@mail.nih.gov.
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Sullivan
mesh_terms: D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000276:immunology / Q000302:isolation & purification; D057134:Antibodies, Neutralizing / Q000008:administration & dosage* / Q000276:immunology / Q000302:isolation & purification; D000914:Antibodies, Viral / Q000008:administration & dosage* / Q000276:immunology / Q000302:isolation & purification; D002986:Clinical Trials as Topic; D004196:Disease Outbreaks; D029043:Ebolavirus / Q000276:immunology*; D005260:Female; D019142:Hemorrhagic Fever, Ebola / Q000453:epidemiology / Q000517:prevention & control*; D006801:Humans; D008251:Macaca; D008297:Male; D008969:Molecular Sequence Data; D017741:Survivors
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral