Evaluating the Mechanisms of Pathogenesis and Antibody-mediated Protection in Enterovirus D68-induced Acute Flaccid Myelitis
Year: 2026
Type: article
Abstract: Enterovirus D68 (EV-D68) is a major cause of acute flaccid myelitis (AFM), a severe neurologic disease in children that can result in sudden paralysis and lifelong disability. Currently, no approved therapies specifically target EV-D68-associated AFM. Monoclonal antibodies (mAbs) represent a promising therapeutic strategy because they combine viral neutralization through the Fab region with immune-cell recruitment through the Fc region. However, the contribution of Fc effector function to protection against EV-D68-induced neurologic disease remains unclear. This study investigated whether Fc effector function enhances protection against AFM using the partially neutralizing mAb EV68-41. Wild-type EV68-41 (EV68-41-WT), which retains Fc effector function, was compared with an Fc-deficient LALAPG variant (EV68-41-LALAPG) in an animal model of EV-D68 infection. Survival and neurologic outcomes were assessed and compared with the potently neutralizing mAb EV68-228. No significant difference in survival was observed between EV68-41-WT and EV68-41-LALAPG, with both providing approximately 60% survival. However, EV68-41-LALAPG-treated mice exhibited higher peak neurologic scores, indicating more severe limb paralysis, compared with EV68-41-WT-treated mice. In contrast, both EV68-228 variants provided 100% survival and complete neurologic protection. These findings demonstrate that Fc effector function can reduce neurologic disease severity even when it does not significantly improve survival. Together, the results suggest that effective mAb therapies for EV-D68-associated AFM should combine potent viral neutralization with Fc-mediated immune recruitment, potentially improving neurologic outcomes and reducing the burden of childhood paralysis.
Source: UNC Libraries
DOI: 10.17615/d42b-s492
Author: Pham Khanh Hoang Luu
Institution: University of North Carolina at Chapel Hill
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7203893237
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