National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
U19 AI117905
米国
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
U19 AI104317
米国
National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI)
P01 HL070831
米国
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
R01 AI011219
米国
引用
ジャーナル: Sci Immunol / 年: 2020 タイトル: Human antibodies neutralize enterovirus D68 and protect against infection and paralytic disease. 著者: Matthew 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 / ...著者: Matthew 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 / 要旨: 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 ...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.