Protective monotherapy against lethal Ebola virus infection by a potently neutralizing antibody

Davide Corti(Università della Svizzera italiana), John Misasi(National Institute of Allergy and Infectious Diseases), Sabue Mulangu(National Institute of Allergy and Infectious Diseases), Daphne A. Stanley(National Institute of Allergy and Infectious Diseases), Masaru Kanekiyo(National Institute of Allergy and Infectious Diseases), Suzanne E. Wollen-Roberts(United States Army Medical Research Institute of Infectious Diseases), Aurélie Ploquin(National Institute of Allergy and Infectious Diseases), Nicole A. Doria‐Rose(National Institute of Allergy and Infectious Diseases), Ryan P. Staupe(National Institute of Allergy and Infectious Diseases), Michael Bailey(National Institute of Allergy and Infectious Diseases), Wei Shi(National Institute of Allergy and Infectious Diseases), Misook Choe(National Institute of Allergy and Infectious Diseases), Hadar Marcus(National Institute of Allergy and Infectious Diseases), Emily A. Thompson(National Institute of Allergy and Infectious Diseases), Alberto Cagigi(National Institute of Allergy and Infectious Diseases), Chiara Silacci(Università della Svizzera italiana), Blanca Fernandez‐Rodriguez(Università della Svizzera italiana), Laurent Perez(Università della Svizzera italiana), Federica Sallusto(Università della Svizzera italiana), Fabrizia Vanzetta, Gloria Agatic, Elisabetta Cameroni, Neville K. Kisalu(National Institute of Biomedical Research), Ingelise J. Gordon(National Institute of Allergy and Infectious Diseases), Julie E. Ledgerwood(National Institute of Allergy and Infectious Diseases), John R. Mascola(National Institute of Allergy and Infectious Diseases), Barney S. Graham(National Institute of Allergy and Infectious Diseases), Jean-Jacques Muyembe-Tamfun(National Institute of Biomedical Research), John C. Trefry(United States Army Medical Research Institute of Infectious Diseases), Antonio Lanzavecchia(ETH Zurich), Nancy J. Sullivan(National Institute of Allergy and Infectious Diseases)
Science
February 26, 2016
Cited by 424

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.


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