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TitleHuman Antibodies Protect against Aerosolized Eastern Equine Encephalitis Virus Infection.
Journal, issue, pagesCell, Vol. 183, Issue 7, Page 1884-1900.e23, Year 2020
Publish dateDec 23, 2020
AuthorsLauren E Williamson / Theron Gilliland / Pramod K Yadav / Elad Binshtein / Robin Bombardi / Nurgun Kose / Rachel S Nargi / Rachel E Sutton / Clarissa L Durie / Erica Armstrong / Robert H Carnahan / Lauren M Walker / Arthur S Kim / Julie M Fox / Michael S Diamond / Melanie D Ohi / William B Klimstra / James E Crowe /
PubMed AbstractEastern 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 ...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.
External linksCell / PubMed:33301709 / PubMed Central
MethodsEM (single particle)
Resolution4.2 - 8.5 Å
Structure data

EMDB-22188:
CryoEM structure of Chimeric Eastern Equine Encephalitis Virus with Fab of EEEV-143 Antibody
Method: EM (single particle) / Resolution: 8.3 Å

EMDB-22223:
CryoEM structure of Chimeric Eastern Equine Encephalitis Virus with Fab of EEEV-33 Antibody
Method: EM (single particle) / Resolution: 7.24 Å

22276

6xo4

EMDB-22276, PDB-6xo4:
CryoEM structure of Eastern Equine Encephalitis (EEEV) VLP
Method: EM (single particle) / Resolution: 4.2 Å

22277

6xob

EMDB-22277, PDB-6xob:
CryoEM structure of Eastern Equine Encephalitis (EEEV) VLP with Fab EEEV-143.
Method: EM (single particle) / Resolution: 8.5 Å

Source
  • eastern equine encephalitis virus
  • homo sapiens (human)
KeywordsVIRUS / VLP / EEEV / VIRAL PROTEIN / Virus/Immune System / Fab / Virus-Immune System complex

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