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Human Antibodies Protect against Aerosolized Eastern Equine Encephalitis Virus Infection.
Williamson, Lauren E; Gilliland, Theron; Yadav, Pramod K; Binshtein, Elad; Bombardi, Robin; Kose, Nurgun; Nargi, Rachel S; Sutton, Rachel E; Durie, Clarissa L; Armstrong, Erica; Carnahan, Robert H; Walker, Lauren M; Kim, Arthur S; Fox, Julie M; Diamond, Michael S; Ohi, Melanie D; Klimstra, William B; Crowe, James E.
Afiliación
  • Williamson LE; Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, TN 37232, USA.
  • Gilliland T; The Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA 165261, USA.
  • Yadav PK; Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA.
  • Binshtein E; The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Bombardi R; The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Kose N; The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Nargi RS; The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Sutton RE; The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Durie CL; Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA.
  • Armstrong E; The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Carnahan RH; The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Walker LM; Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, TN 37232, USA.
  • Kim AS; Department of Medicine, Washington University, St. Louis, MO 63110, USA; Department of Pathology and Immunology, Washington University, St. Louis, MO 63110, USA.
  • Fox JM; Department of Medicine, Washington University, St. Louis, MO 63110, USA.
  • Diamond MS; Department of Medicine, Washington University, St. Louis, MO 63110, USA; Department of Pathology and Immunology, Washington University, St. Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University, St. Louis, MO 63110, USA.
  • Ohi MD; Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA; Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
  • Klimstra WB; The Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA 165261, USA; Department of Immunology, University of Pittsburgh, Pittsburgh, PA 165261, USA.
  • Crowe JE; Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, TN 37232, USA; The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA. Electronic a
Cell ; 183(7): 1884-1900.e23, 2020 12 23.
Article en En | MEDLINE | ID: mdl-33301709
ABSTRACT
Eastern equine encephalitis virus (EEEV) is one of the most virulent viruses endemic to North America. No licensed vaccines or antiviral therapeutics are available to combat this infection, which has recently shown an increase in human cases. Here, we characterize human monoclonal antibodies (mAbs) isolated from a survivor of natural EEEV infection with potent (<20 pM) inhibitory activity of EEEV. Cryo-electron microscopy reconstructions of two highly neutralizing mAbs, EEEV-33 and EEEV-143, were solved in complex with chimeric Sindbis/EEEV virions to 7.2 Å and 8.3 Å, respectively. The mAbs recognize two distinct antigenic sites that are critical for inhibiting viral entry into cells. EEEV-33 and EEEV-143 protect against disease following stringent lethal aerosol challenge of mice with highly pathogenic EEEV. These studies provide insight into the molecular basis for the neutralizing human antibody response against EEEV and can facilitate development of vaccines and candidate antibody therapeutics.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Aerosoles / Virus de la Encefalitis Equina del Este / Encefalomielitis Equina / Anticuerpos Monoclonales / Anticuerpos Antivirales Límite: Adult / Animals / Female / Humans Idioma: En Revista: Cell Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Aerosoles / Virus de la Encefalitis Equina del Este / Encefalomielitis Equina / Anticuerpos Monoclonales / Anticuerpos Antivirales Límite: Adult / Animals / Female / Humans Idioma: En Revista: Cell Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos
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