Cell
Volume 183, Issue 7, 23 December 2020, Pages 1884-1900.e23
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Article
Human Antibodies Protect against Aerosolized Eastern Equine Encephalitis Virus Infection

https://doi.org/10.1016/j.cell.2020.11.011Get rights and content
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Highlights

  • Potent human anti-EEEV monoclonal antibodies were isolated from an EEEV survivor

  • Fabs neutralized virus, but bivalent IgG was optimal for neutralization

  • Antibodies inhibit virus entry by stabilization of virus particles

  • EEEV-33 (IgG) and EEEV-143 (IgA) protected against aerosolized EEEV challenge

Summary

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

encephalitis
Eastern equine
human antibodies
monoclonal
neutralizing
prophylaxis
therapy
aerosol

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