A Vaccine for Acute Flaccid Myelitis

SUMMARYIn 2014 the United States experienced an outbreak of a previously unknown neurological disease with
polio-like symptoms later known as acute flaccid myelitis (AFM). A biennial surge in cases of AFM in 2016 and
2018 has alarmed public health officials. Since then, rapidly accumulating clinical, immunological, and
epidemiological evidence has pointed to EV-D68 as the major causative agent of the seasonal AFM outbreaks
in the US. EV-D68 is an airborne respiratory virus and as such it is difficult to prevent its transmission. This and
the fact that there is currently no antiviral treatment for this ailment underscore the importance of developing a
vaccine for EV-D68. The urgency of this need also stems from the fact that vaccine development takes time, and
evidence confirming EV-D68 as the etiological agent of AFM suggests that cases may increase again during
2020.The long-term goal of this project is to generate live attenuated variants of EV-D68 and evaluate their
safety and effectiveness as potential vaccines. Our objective is to design a live attenuated EV-D68 vaccine
candidate following the same combinatorial approach that we recently developed to generate nOPV2, an
improved oral polio vaccine derived from Sabin Type 2 vaccine currently in Phase II clinical trials. nOPV2 exhibits
the same overall replication strength, fitness in vaccinees and immunogenicity of Sabin, but is significantly safer
because it has greater genetic stability and hence a much lower rate of reversion to virulence than Sabin’s OPV.NARRATIVE
EV-D68 is an emerging enteric virus spreading through the world and believed to be the agent that causes Acute
Flaccid Myelitis (AFM). We propose to develop EV-D68 live-attenuated oral vaccine candidates capable of
eliciting robust mucosal immunity, to prevent EV-D68 transmission through the community.