Thrasher Research Fund - Medical research grants to improve the lives of children

Project Details

Early Career

Status: Funded - Closed

The role of human antibody in enterovirus D68 associated acute flaccid myelitis

Matthew Vogt, MD, PhD


BACKGROUND: Acute flaccid myelitis (AFM) is a poliomyelitis-like illness consisting of acute onset flaccid limb weakness that is increasing steadily in incidence in the United States to 236 cases during an outbreak in 2018. Enterovirus D68 (EV-D68), a respiratory virus, is the main pathogen associated with AFM outbreaks. GAP: Seroepidemiology studies in adults from across the world show essentially universal presence of serum neutralizing antibodies to EV-D68, but children do not exhibit this universal seropositivity. While circulating neutralizing antibodies do not prevent respiratory infection with EV-D68, it is not known whether such antibodies can prevent AFM in EV-D68 infected patients. HYPOTHESIS: We hypothesize that circulating EV-D68 neutralizing antibodies can protect against AFM in EV-D68 infected patients, similar to the way in which poliovirus vaccines induce systemic antibodies that protect against poliomyelitis disease but not enteral poliovirus infection. METHODS: Both polyclonal antibodies from human serum and monoclonal antibodies (mAbs) isolated from human memory B cells will be tested for their ability to block EV-D68 infection in vitro and block AFM-like disease in vivo. RESULTS: So far, we have shown that two mAbs, termed EV68-105 and EV68-228, potently neutralizes diverse clinical isolates of EV-D68 in vitro. When given as either prophylaxis before or treatment after EV-D68 inoculation, both mAbs protects mice from both respiratory disease and AFM-like paralytic disease, whereas equivalent doses of polyclonal human immunoglobulin (IVIG) protect only partially. IMPACT: We are already working with industry collaborators to develop EV-D68 neutralizing human mAbs as a therapeutic agent for people with severe respiratory disease or AFM in the context of EV-D68 infection. Website Link: https://www.vogtviruslab.comOptional/Additional Comments For both patients and physicians, the following websites are of great use for questions about EV-D68 and AFM: Siegel Rare Neuroimmune Association:

Supervising Institution:
University of North Carolina at Chapel Hill

Mark Heise

Project Location:
North Carolina

Award Amount: