2. Academic Validation
  3. Human Antibodies Protect against Aerosolized Eastern Equine Encephalitis Virus Infection

Human Antibodies Protect against Aerosolized Eastern Equine Encephalitis Virus Infection

  • Cell. 2020 Dec 23;183(7):1884-1900.e23. doi: 10.1016/j.cell.2020.11.011.
Lauren E Williamson 1,  Theron Gilliland Jr 2,  Pramod K Yadav 3,  Elad Binshtein 4,  Robin Bombardi 4,  Nurgun Kose 4,  Rachel S Nargi 4,  Rachel E Sutton 4,  Clarissa L Durie 3,  Erica Armstrong 4,  Robert H Carnahan 4,  Lauren M Walker 1,  Arthur S Kim 5,  Julie M Fox 6,  Michael S Diamond 7,  Melanie D Ohi 8,  William B Klimstra 9,  James E Crowe Jr 10
Affiliations

Affiliations

  • 1 Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, TN 37232, USA.
  • 2 The Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA 165261, USA.
  • 3 Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA.
  • 4 The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • 5 Department of Medicine, Washington University, St. Louis, MO 63110, USA; Department of Pathology and Immunology, Washington University, St. Louis, MO 63110, USA.
  • 6 Department of Medicine, Washington University, St. Louis, MO 63110, USA.
  • 7 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.
  • 8 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.
  • 9 The Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA 165261, USA; Department of Immunology, University of Pittsburgh, Pittsburgh, PA 165261, USA.
  • 10 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 address: james.crowe@vumc.org.
PMID: 33301709 DOI: 10.1016/j.cell.2020.11.011
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.

Keywords

Eastern equine; aerosol; encephalitis; human antibodies; monoclonal; neutralizing; prophylaxis; therapy.

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