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

  • Science. 2016 Mar 18;351(6279):1339-42. doi: 10.1126/science.aad5224.
Davide Corti  1 ,  John Misasi  2 ,  Sabue Mulangu  2 ,  Daphne A Stanley  2 ,  Masaru Kanekiyo  2 ,  Suzanne Wollen  3 ,  Aurélie Ploquin  2 ,  Nicole A Doria-Rose  2 ,  Ryan P Staupe  2 ,  Michael Bailey  2 ,  Wei Shi  2 ,  Misook Choe  2 ,  Hadar Marcus  2 ,  Emily A Thompson  2 ,  Alberto Cagigi  2 ,  Chiara Silacci  4 ,  Blanca Fernandez-Rodriguez  4 ,  Laurent Perez  4 ,  Federica Sallusto  4 ,  Fabrizia Vanzetta  5 ,  Gloria Agatic  5 ,  Elisabetta Cameroni  5 ,  Neville Kisalu  6 ,  Ingelise Gordon  2 ,  Julie E Ledgerwood  2 ,  John R Mascola  2 ,  Barney S Graham  2 ,  Jean-Jacques Muyembe-Tamfun  6 ,  John C Trefry  3 ,  Antonio Lanzavecchia  7 ,  Nancy J Sullivan  8
Affiliations
  • 1. Institute for Research in Biomedicine, Università della Svizzera Italiana, CH-6500 Bellinzona, Switzerland. Humabs BioMed SA, 6500 Bellinzona, Switzerland.
  • 2. Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
  • 3. U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA.
  • 4. Institute for Research in Biomedicine, Università della Svizzera Italiana, CH-6500 Bellinzona, Switzerland.
  • 5. Humabs BioMed SA, 6500 Bellinzona, Switzerland.
  • 6. National Institute for Biomedical Research, National Laboratory of Public Health, Kinshasa B.P. 1197, Democratic Republic of the Congo.
  • 7. Institute for Research in Biomedicine, Università della Svizzera Italiana, CH-6500 Bellinzona, Switzerland. Institute of Microbiology, ETH Zürich, CH-8093 Zürich, Switzerland.
  • 8. Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA. [email protected].
PMID: 26917593 DOI: 10.1126/science.aad5224
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.

Products