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Cross-Reactive and Potent Neutralizing Antibody Responses in Human Survivors of Natural Ebolavirus Infection.
Flyak, Andrew I; Shen, Xiaoli; Murin, Charles D; Turner, Hannah L; David, Joshua A; Fusco, Marnie L; Lampley, Rebecca; Kose, Nurgun; Ilinykh, Philipp A; Kuzmina, Natalia; Branchizio, Andre; King, Hannah; Brown, Leland; Bryan, Christopher; Davidson, Edgar; Doranz, Benjamin J; Slaughter, James C; Sapparapu, Gopal; Klages, Curtis; Ksiazek, Thomas G; Saphire, Erica Ollmann; Ward, Andrew B; Bukreyev, Alexander; Crowe, James E.
Affiliation
  • Flyak AI; Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, TN 37232, USA.
  • Shen X; Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA.
  • Murin CD; 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.
  • Turner HL; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • David JA; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Fusco ML; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Lampley R; Vanderbilt Vaccine Center, Vanderbilt University, Nashville, TN 37232, USA.
  • Kose N; Vanderbilt Vaccine Center, Vanderbilt University, Nashville, TN 37232, USA.
  • Ilinykh PA; Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA.
  • Kuzmina N; Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA.
  • Branchizio A; Vanderbilt Vaccine Center, Vanderbilt University, Nashville, TN 37232, USA.
  • King H; Vanderbilt Vaccine Center, Vanderbilt University, Nashville, TN 37232, USA.
  • Brown L; Vanderbilt Vaccine Center, Vanderbilt University, Nashville, TN 37232, USA.
  • Bryan C; Integral Molecular Inc., Philadelphia, PA 19104, USA.
  • Davidson E; Integral Molecular Inc., Philadelphia, PA 19104, USA.
  • Doranz BJ; Integral Molecular Inc., Philadelphia, PA 19104, USA.
  • Slaughter JC; Vanderbilt Vaccine Center, Vanderbilt University, Nashville, TN 37232, USA; Department of Biostatistics, Vanderbilt University, Nashville, TN 37232, USA.
  • Sapparapu G; Vanderbilt Vaccine Center, Vanderbilt University, Nashville, TN 37232, USA.
  • Klages C; Galveston National Laboratory, Galveston, TX 77550, USA.
  • Ksiazek TG; 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.
  • Saphire EO; 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.
  • Ward AB; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Bukreyev A; 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.
  • Crowe JE; 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
Cell ; 164(3): 392-405, 2016 Jan 28.
Article in En | MEDLINE | ID: mdl-26806128
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Survivors / Hemorrhagic Fever, Ebola / Ebolavirus / Antibodies, Neutralizing / Antibodies, Monoclonal Limits: Animals / Humans Country/Region as subject: Africa Language: En Journal: Cell Year: 2016 Type: Article Affiliation country: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Survivors / Hemorrhagic Fever, Ebola / Ebolavirus / Antibodies, Neutralizing / Antibodies, Monoclonal Limits: Animals / Humans Country/Region as subject: Africa Language: En Journal: Cell Year: 2016 Type: Article Affiliation country: United States