Michael J Rudy, Courtney J Wilson, Brendan Hinckley, Danielle C Baker, Joshua M Royal, Marshall P Hoke, Miles B Brennan, Matthew R Vogt, Penny Clarke, Kenneth L Tyler
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引用次数: 0
Abstract
In 2014, 2016, and 2018, infection with enterovirus D68 (EV-D68) was associated with outbreaks of a poliomyelitis-like paralytic syndrome, called acute flaccid myelitis (AFM). While only a small fraction of patients infected with EV-D68 developed AFM, this subgroup of patients does not typically seek treatment until after the onset of neurological symptoms. There are currently no approved human monoclonal antibody therapies or vaccines available for EV-D68. Here, we show that a monoclonal antibody, EV68-228-N, can quickly stop the progression of paralysis in a mouse model of AFM, even when treatment is initiated after the onset of paralysis. We found that EV68-228-N effectively halted the progression of paralysis when tested against both 2014 and 2016 EV-D68 isolates in an immunocompetent mouse model of AFM. All animal experiments were conducted in a blinded fashion. The IC50 of EV68-228-N against 2014 and 2016 EV-D68 isolates was confirmed in vitro to be less than 330 ng/mL, and EV68-228-N was found to be equally effective at neutralizing 2018 and 2022 viral isolates without any evidence of emerging resistance. We further show that, following infection with EV-D68, mice treated with EV68-228-N have more surviving motor neurons in the spinal cord's lumbar enlargement than control treated animals. Taken together, this work suggests that EV68-228-N treatment has the potential to halt the progression of paralysis in AFM patients who present at the clinic with neurologic symptoms and that EV68-228-N will retain neutralization potential against emerging EV-D68 isolates.
Importance: Enterovirus D-68 (EV-D68) associated acute flaccid myelitis (AFM) is an emergent poliomyelitis-like illness occurring predominantly in children. There are currently no proven effective therapies. We describe the use of a human monoclonal antibody (EV68-228-N) in a murine model of EV-D68 AFM in which therapy prevents progression of paralysis even when treatment is instituted after onset of weakness.
Clinical trials: This study is registered with ClinicalTrials.gov as NCT06444048.
期刊介绍：
mBio® is ASM''s first broad-scope, online-only, open access journal. mBio offers streamlined review and publication of the best research in microbiology and allied fields.
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