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Human antibodies neutralize enterovirus D68 and protect against infection and paralytic disease.

ABSTRACT: 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.

SUBMITTER: Vogt MR

PROVIDER: S-EPMC7418079 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Human antibodies neutralize enterovirus D68 and protect against infection and paralytic disease.

Vogt Matthew R MR Fu Jianing J Kose Nurgun N Williamson Lauren E LE Bombardi Robin R Setliff Ian I Georgiev Ivelin S IS Klose Thomas T Rossmann Michael G MG Bochkov Yury A YA Gern James E JE Kuhn Richard J RJ Crowe James E JE

Science immunology 20200701 49

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 d ...[more]

PMID: 32620559

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Human antibodies neutralize enterovirus D68 and protect against infection and paralytic disease.

Publications

Human antibodies neutralize enterovirus D68 and protect against infection and paralytic disease.

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