Key result
Monoclonal antibody EV68-228 neutralizes diverse EV-D68 strains and prevents respiratory and neurologic disease in mice.
Why the study?
Enterovirus D68 causes outbreaks of respiratory illness and acute flaccid myelitis, but there are no licensed therapies to prevent or treat infection or disease.
Do human monoclonal antibodies neutralize enterovirus D68 and protect against respiratory and neurologic disease in a mouse model?
Do human monoclonal antibodies neutralize enterovirus D68 and protect against respiratory and neurologic disease in a mouse model?
Human monoclonal antibodies potently neutralize EV-D68 and protect mice from respiratory and neurologic disease, suggesting they are candidates for clinical use to prevent or treat acute flaccid myelitis.
May support EV68-228 development for EV-D68; leaves open translation to human AFM trials.
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.
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Vogt et al. (2020) studied Enterovirus D68 infection (n=12). EV68-228 monoclonal antibody vs. IVIG or placebo was evaluated on In vitro neutralization and in vivo protection against EV-D68 in mice. The human monoclonal antibody EV68-228 potently neutralized diverse EV-D68 variants and protected mice from respiratory and neurologic disease when administered prophylactically or therapeutically.
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