Project Details

Early Career

Status: Funded - Open

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

Matthew Vogt, MD, PhD

Summary

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 one mAb, termed EV68-228, potently neutralizes diverse clinical isolates of EV-D68 in vitro. When given as either prophylaxis before or treatment after EV-D68 inoculation, mAb EV68-228 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 mAb EV68-228 as a therapeutic agent for people with severe respiratory disease or AFM in the context of EV-D68 infection.

Website Link: https://www.vumc.org/crowe-lab/person/matthew-vogt-md-phd

Optional/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: https://wearesrna.org/

CDC: https://www.cdc.gov/non-polio-enterovirus/about/ev-d68.html

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 one mAb, termed EV68-228, potently neutralizes diverse clinical isolates of EV-D68 in vitro. When given as either prophylaxis before or treatment after EV-D68 inoculation, mAb EV68-228 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 mAb EV68-228 as a therapeutic agent for people with severe respiratory disease or AFM in the context of EV-D68 infection.

Website Link: https://www.vumc.org/crowe-lab/person/matthew-vogt-md-phd

Optional/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: https://wearesrna.org/

CDC: https://www.cdc.gov/non-polio-enterovirus/about/ev-d68.html