RT Journal Article
SR Electronic
T1 Human antibodies neutralize enterovirus D68 and protect against infection and paralytic disease
JF Science Immunology
JO Sci. Immunol.
FD American Association for the Advancement of Science
SP eaba4902
DO 10.1126/sciimmunol.aba4902
VO 5
IS 49
A1 Vogt, Matthew R.
A1 Fu, Jianing
A1 Kose, Nurgun
A1 Williamson, Lauren E.
A1 Bombardi, Robin
A1 Setliff, Ian
A1 Georgiev, Ivelin S.
A1 Klose, Thomas
A1 Rossmann, Michael G.
A1 Bochkov, Yury A.
A1 Gern, James E.
A1 Kuhn, Richard J.
A1 Crowe, James E.
YR 2020
UL http://immunology.sciencemag.org/content/5/49/eaba4902.abstract
AB Enterovirus D68 (EV-D68) is a human respiratory virus associated with acute flaccid myelitis, a rare paralytic disease primarily occurring in young children. To develop a potential therapeutic agent for this emerging disease, Vogt et al. screened B cells from participants with past EV-D68 infection for virus-binding antibodies and isolated a series of human monoclonal antibodies (mAbs). One mAb that neutralized virus from all EV-D68 clades tested was shown by cryo–electron microscopy to bind a conformational epitope on the viral capsid surface. This highly cross-reactive mAb also protected immunodeficient mice from EV-D68–induced respiratory and neurological disease when given as prophylaxis or therapy. This research sets the stage for clinical testing of antibody therapy in patients with severe EV-D68 disease when the next virus outbreak occurs.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.