title: Cross-Reactive and Potent Neutralizing Antibody Responses in Human Survivors of Natural Ebolavirus Infection.
abstract: Recent studies have suggested that antibody-mediated protection against the Ebolaviruses may be achievable, but little is known about whether or not antibodies can confer cross-reactive protection against viruses belonging to diverse Ebolavirus species, such as Ebola virus (EBOV), Sudan virus (SUDV), and Bundibugyo virus (BDBV). We isolated a large panel of human monoclonal antibodies (mAbs) against BDBV glycoprotein (GP) using peripheral blood B cells from survivors of the 2007 BDBV outbreak in Uganda. We determined that a large proportion of mAbs with potent neutralizing activity against BDBV bind to the glycan cap and recognize diverse epitopes within this major antigenic site. We identified several glycan cap-specific mAbs that neutralized multiple ebolaviruses, including SUDV, and a cross-reactive mAb that completely protected guinea pigs from the lethal challenge with heterologous EBOV. Our results provide a roadmap to develop a single antibody-based treatment effective against multiple Ebolavirus infections.
authors.affiliation: Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: Andrew I
authors.initials: AI
authors.lastname: Flyak
authors.affiliation: Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Shen
authors.affiliation: Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Charles D
authors.initials: CD
authors.lastname: Murin
authors.affiliation: Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Hannah L
authors.initials: HL
authors.lastname: Turner
authors.affiliation: Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Joshua A
authors.initials: JA
authors.lastname: David
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Marnie L
authors.initials: ML
authors.lastname: Fusco
authors.affiliation: Vanderbilt Vaccine Center, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Lampley
authors.affiliation: Vanderbilt Vaccine Center, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: Nurgun
authors.initials: N
authors.lastname: Kose
authors.affiliation: Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Philipp A
authors.initials: PA
authors.lastname: Ilinykh
authors.affiliation: Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Natalia
authors.initials: N
authors.lastname: Kuzmina
authors.affiliation: Vanderbilt Vaccine Center, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: Andre
authors.initials: A
authors.lastname: Branchizio
authors.affiliation: Vanderbilt Vaccine Center, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: Hannah
authors.initials: H
authors.lastname: King
authors.affiliation: Vanderbilt Vaccine Center, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: Leland
authors.initials: L
authors.lastname: Brown
authors.affiliation: Integral Molecular Inc., Philadelphia, PA 19104, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Bryan
authors.affiliation: Integral Molecular Inc., Philadelphia, PA 19104, USA.
authors.forename: Edgar
authors.initials: E
authors.lastname: Davidson
authors.affiliation: Integral Molecular Inc., Philadelphia, PA 19104, USA.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Doranz
authors.affiliation: Vanderbilt Vaccine Center, Vanderbilt University, Nashville, TN 37232, USA; Department of Biostatistics, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: James C
authors.initials: JC
authors.lastname: Slaughter
authors.affiliation: Vanderbilt Vaccine Center, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: Gopal
authors.initials: G
authors.lastname: Sapparapu
authors.affiliation: Galveston National Laboratory, Galveston, TX 77550, USA.
authors.forename: Curtis
authors.initials: C
authors.lastname: Klages
authors.affiliation: Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA; Galveston National Laboratory, Galveston, TX 77550, USA.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Ksiazek
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA; The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Erica Ollmann
authors.initials: EO
authors.lastname: Saphire
authors.affiliation: Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Ward
authors.affiliation: Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA; Galveston National Laboratory, Galveston, TX 77550, USA. Electronic address: alexander.bukreyev@utmb.edu.
authors.forename: Alexander
authors.initials: A
authors.lastname: Bukreyev
authors.affiliation: Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, TN 37232, USA; Department of Pediatrics, Vanderbilt University, Nashville, TN 37232, USA; Vanderbilt Vaccine Center, Vanderbilt University, Nashville, TN 37232, USA. Electronic address: james.crowe@vanderbilt.edu.
authors.forename: James E
authors.initials: JE
authors.lastname: Crowe
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000276:immunology*; D003429:Cross Reactions; D004195:Disease Models, Animal; D029043:Ebolavirus / Q000276:immunology*; D018604:Epitope Mapping; D006168:Guinea Pigs; D019142:Hemorrhagic Fever, Ebola / Q000276:immunology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D008958:Models, Molecular; D016296:Mutagenesis; D017741:Survivors; D014454:Uganda
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing