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

Autor:	Vogt MR; Department of Pediatrics (Infectious Diseases), Vanderbilt University Medical Center, Nashville, TN, USA., Fu J; Department of Biological Sciences and Purdue Institute of Inflammation, Immunology, and Infectious Disease, Purdue University, West Lafayette, IN, USA., Kose N; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN, USA., Williamson LE; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA., Bombardi R; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN, USA., Setliff I; Program in Chemical and Physical Biology, Vanderbilt University, Nashville, TN, USA., Georgiev IS; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA., Klose T; Department of Biological Sciences and Purdue Institute of Inflammation, Immunology, and Infectious Disease, Purdue University, West Lafayette, IN, USA., Rossmann MG; Department of Biological Sciences and Purdue Institute of Inflammation, Immunology, and Infectious Disease, Purdue University, West Lafayette, IN, USA., Bochkov YA; Department of Pediatrics, University of Wisconsin-Madison, Madison, WI, USA., Gern JE; Department of Pediatrics, University of Wisconsin-Madison, Madison, WI, USA.; Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA., Kuhn RJ; Department of Biological Sciences and Purdue Institute of Inflammation, Immunology, and Infectious Disease, Purdue University, West Lafayette, IN, USA., Crowe JE Jr; Department of Pediatrics (Infectious Diseases), Vanderbilt University Medical Center, Nashville, TN, USA. james.crowe@vumc.org.; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.; Program in Chemical and Physical Biology, Vanderbilt University, Nashville, TN, USA.
Jazyk:	angličtina
Zdroj:	Science immunology [Sci Immunol] 2020 Jul 03; Vol. 5 (49).
DOI:	10.1126/sciimmunol.aba4902
Abstrakt:	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. (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
Databáze:	MEDLINE
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