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TitleHuman antibodies neutralize enterovirus D68 and protect against infection and paralytic disease.
Journal, issue, pagesSci Immunol, Vol. 5, Issue 49, Year 2020
Publish dateJul 3, 2020
AuthorsMatthew R Vogt / Jianing Fu / Nurgun Kose / Lauren E Williamson / Robin Bombardi / Ian Setliff / Ivelin S Georgiev / Thomas Klose / Michael G Rossmann / Yury A Bochkov / James E Gern / Richard J Kuhn / James E Crowe /
PubMed AbstractEnterovirus D68 (EV-D68) causes outbreaks of respiratory illness, and there is increasing evidence that it causes outbreaks of acute flaccid myelitis (AFM). There are no licensed therapies to prevent ...Enterovirus D68 (EV-D68) causes outbreaks of respiratory illness, and there is increasing evidence that it causes outbreaks of acute flaccid myelitis (AFM). There are no licensed therapies to prevent or treat EV-D68 infection or AFM disease. We isolated a panel of EV-D68-reactive human monoclonal antibodies that recognize diverse antigenic variants from participants with prior infection. One potently neutralizing cross-reactive antibody, EV68-228, protected mice from respiratory and neurologic disease when given either before or after infection. Cryo-electron microscopy studies revealed that EV68-228 and another potently neutralizing antibody (EV68-159) bound around the fivefold or threefold axes of symmetry on virion particles, respectively. The structures suggest diverse mechanisms of action by these antibodies. The high potency and effectiveness observed in vivo suggest that antibodies are a mechanistic correlate of protection against AFM disease and are candidates for clinical use in humans with EV-D68 infection.
External linksSci Immunol / PubMed:32620559 / PubMed Central
MethodsEM (single particle)
Resolution2.9 - 3.1 Å
Structure data

21647

6wds

EMDB-21647, PDB-6wds:
Enterovirus D68 in complex with human monoclonal antibody EV68-159
Method: EM (single particle) / Resolution: 2.9 Å

21648

6wdt

EMDB-21648, PDB-6wdt:
Enterovirus D68 in complex with human monoclonal antibody EV68-228
Method: EM (single particle) / Resolution: 3.1 Å

Source
  • homo sapiens (human)
  • enterovirus d68
KeywordsVIRUS/IMMUNE SYSTEM / virus / enterovirus / antibody / Structural Genomics / Center for Structural Genomics of Infectious Diseases / CSGID / VIRUS-IMMUNE SYSTEM complex

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