title: Discovery of an antibody for pan-ebolavirus therapy.
abstract: During the latest outbreak of Ebola virus disease in West Africa, monoclonal antibody therapy (e.g., ZMapp) was utilized to treat patients. However, due to the antigenic differences among the five ebolavirus species, the current therapeutic monoclonal antibodies are only effective against viruses of the species Zaire ebolavirus. Although this particular species has indeed caused the majority of human infections in Central and, recently, West Africa, other ebolavirus species (e.g., Sudan ebolavirus and Bundibugyo ebolavirus) have also repeatedly caused outbreaks in Central Africa and thus should not be neglected in the development of countermeasures against ebolaviruses. Here we report the generation of an ebolavirus glycoprotein-specific monoclonal antibody that effectively inhibits cellular entry of representative isolates of all known ebolavirus species in vitro and show its protective efficacy in mouse models of ebolavirus infections. This novel neutralizing monoclonal antibody targets a highly conserved internal fusion loop in the glycoprotein molecule and prevents membrane fusion of the viral envelope with cellular membranes. The discovery of this highly cross-neutralizing antibody provides a promising option for broad-acting ebolavirus antibody therapy and will accelerate the design of improved vaccines that can selectively elicit cross-neutralizing antibodies against multiple species of ebolaviruses.
authors: Division of Global Epidemiology, Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan.
authors: Wakako
authors: W
authors: Furuyama
authors: Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, Montana, USA.
authors: Andrea
authors: A
authors: Marzi
authors: Department of Cell Physiology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
authors: Asuka
authors: A
authors: Nanbo
authors: Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, Montana, USA.
authors: Elaine
authors: E
authors: Haddock
authors: Division of Global Epidemiology, Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan.
authors: Junki
authors: J
authors: Maruyama
authors: Division of Global Epidemiology, Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan.
authors: Hiroko
authors: H
authors: Miyamoto
authors: Division of Global Epidemiology, Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan.
authors: Manabu
authors: M
authors: Igarashi
authors: Division of Global Epidemiology, Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan.
authors: Reiko
authors: R
authors: Yoshida
authors: Division of Global Epidemiology, Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan.
authors: Osamu
authors: O
authors: Noyori
authors: Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, Montana, USA.
authors: Heinz
authors: H
authors: Feldmann
authors: Division of Global Epidemiology, Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan.
authors: Ayato
authors: A
authors: Takada
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D057134:Antibodies, Neutralizing / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D029043:Ebolavirus / Q000378:metabolism; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D005260:Female; D019142:Hemorrhagic Fever, Ebola / Q000188:drug therapy* / Q000401:mortality / Q000662:veterinary; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D053633:Receptor, Interferon alpha-beta / Q000172:deficiency / Q000235:genetics; D016415:Sequence Alignment; D015996:Survival Rate; D014709:Vero Cells; D053586:Virus Internalization / Q000187:drug effects
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000939:Epitopes; D053633:Receptor, Interferon alpha-beta