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Systematic Analysis of Monoclonal Antibodies against Ebola Virus GP Defines Features that Contribute to Protection.
Saphire, Erica Ollmann; Schendel, Sharon L; Fusco, Marnie L; Gangavarapu, Karthik; Gunn, Bronwyn M; Wec, Anna Z; Halfmann, Peter J; Brannan, Jennifer M; Herbert, Andrew S; Qiu, Xiangguo; Wagh, Kshitij; He, Shihua; Giorgi, Elena E; Theiler, James; Pommert, Kathleen B J; Krause, Tyler B; Turner, Hannah L; Murin, Charles D; Pallesen, Jesper; Davidson, Edgar; Ahmed, Rafi; Aman, M Javad; Bukreyev, Alexander; Burton, Dennis R; Crowe, James E; Davis, Carl W; Georgiou, George; Krammer, Florian; Kyratsous, Christos A; Lai, Jonathan R; Nykiforuk, Cory; Pauly, Michael H; Rijal, Pramila; Takada, Ayato; Townsend, Alain R; Volchkov, Viktor; Walker, Laura M; Wang, Cheng-I; Zeitlin, Larry; Doranz, Benjamin J; Ward, Andrew B; Korber, Bette; Kobinger, Gary P; Andersen, Kristian G; Kawaoka, Yoshihiro; Alter, Galit; Chandran, Kartik; Dye, John M.
Afiliación
  • Saphire EO; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: erica@scripps.edu.
  • Schendel SL; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Fusco ML; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Gangavarapu K; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Gunn BM; Ragon Institute, Cambridge, MA 02139, USA.
  • Wec AZ; Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
  • Halfmann PJ; Division of Pathobiological Sciences, University of Wisconsin, Madison, WI 53706, USA.
  • Brannan JM; Division of Virology, United States Army Research Institute for Infectious Diseases, Ft. Detrick, MD 21702, USA.
  • Herbert AS; Division of Virology, United States Army Research Institute for Infectious Diseases, Ft. Detrick, MD 21702, USA.
  • Qiu X; National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg R3E 3R2, Canada.
  • Wagh K; Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
  • He S; National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg R3E 3R2, Canada.
  • Giorgi EE; Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
  • Theiler J; Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
  • Pommert KBJ; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Krause TB; Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
  • Turner HL; Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Murin CD; Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Pallesen J; Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Davidson E; Integral Molecular, Philadelphia, PA 19104, USA.
  • Ahmed R; Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
  • Aman MJ; Integrated BioTherapeutics, Rockville, MD 20850, USA.
  • Bukreyev A; Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77555, USA.
  • Burton DR; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Crowe JE; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Davis CW; Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
  • Georgiou G; Department of Chemical Engineering, University of Texas at Austin, Austin, TX 78712, USA.
  • Krammer F; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Kyratsous CA; Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591, USA.
  • Lai JR; Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
  • Nykiforuk C; Emergent BioSolutions, Winnipeg, Manitoba, R3T 5Y3, Canada.
  • Pauly MH; Mapp Biopharmaceutical, San Diego, CA 92121, USA.
  • Rijal P; Human Immunology Unit, University of Oxford, Oxford OX3 9DS, UK.
  • Takada A; Research Center for Zoonosis Control, Hokkaido University, Sapporo 001-0020, Japan.
  • Townsend AR; Human Immunology Unit, University of Oxford, Oxford OX3 9DS, UK.
  • Volchkov V; INSERM CNRS, Université Lyon, Lyon, France.
  • Walker LM; Adimab, LLC. Lebanon, NH 03766, USA.
  • Wang CI; Singapore Immunology Network, Agency for Science, Technology and Research (A(∗)STAR), Biopolis 138648, Singapore.
  • Zeitlin L; Mapp Biopharmaceutical, San Diego, CA 92121, USA.
  • Doranz BJ; Integral Molecular, Philadelphia, PA 19104, USA.
  • Ward AB; Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Korber B; Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
  • Kobinger GP; Département de Microbiologie-Infectiologie et d'Immunologie, Médecine, Université Laval Quebec, G1V 046 Canada. Electronic address: gary.kobinger@crchudequebec.ulaval.ca.
  • Andersen KG; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: andersen@scripps.edu.
  • Kawaoka Y; Division of Pathobiological Sciences, University of Wisconsin, Madison, WI 53706, USA. Electronic address: kawaokay@svm.vetmed.wisc.edu.
  • Alter G; Ragon Institute, Cambridge, MA 02139, USA. Electronic address: galter@mgh.harvard.edu.
  • Chandran K; Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. Electronic address: kartik.chandran@einstein.yu.edu.
  • Dye JM; Division of Virology, United States Army Research Institute for Infectious Diseases, Ft. Detrick, MD 21702, USA. Electronic address: john.m.dye1.civ@mail.mil.
Cell ; 174(4): 938-952.e13, 2018 08 09.
Article en En | MEDLINE | ID: mdl-30096313
ABSTRACT
Antibodies are promising post-exposure therapies against emerging viruses, but which antibody features and in vitro assays best forecast protection are unclear. Our international consortium systematically evaluated antibodies against Ebola virus (EBOV) using multidisciplinary assays. For each antibody, we evaluated epitopes recognized on the viral surface glycoprotein (GP) and secreted glycoprotein (sGP), readouts of multiple neutralization assays, fraction of virions left un-neutralized, glycan structures, phagocytic and natural killer cell functions elicited, and in vivo protection in a mouse challenge model. Neutralization and induction of multiple immune effector functions (IEFs) correlated most strongly with protection. Neutralization predominantly occurred via epitopes maintained on endosomally cleaved GP, whereas maximal IEF mapped to epitopes farthest from the viral membrane. Unexpectedly, sGP cross-reactivity did not significantly influence in vivo protection. This comprehensive dataset provides a rubric to evaluate novel antibodies and vaccine responses and a roadmap for therapeutic development for EBOV and related viruses.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Glicoproteínas de Membrana / Fiebre Hemorrágica Ebola / Ebolavirus / Anticuerpos Monoclonales / Epítopos Límite: Animals Idioma: En Año: 2018 Tipo del documento: Article
Texto completo
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Glicoproteínas de Membrana / Fiebre Hemorrágica Ebola / Ebolavirus / Anticuerpos Monoclonales / Epítopos Límite: Animals Idioma: En Año: 2018 Tipo del documento: Article