In 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 Sabins OPV.
Public Health Relevance Statement: 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.
Project Terms: 3-Dimensional; 5' Untranslated Regions; acute flaccid myelitis; Antiviral Agents; Attenuated; Attenuated Live Virus Vaccine; Attenuated Vaccines; attenuation; Biological; Biological Models; Capsid; Capsid Proteins; Chimera organism; Clinical; combinatorial; Communities; design; Development; Disease; Disease Outbreaks; Effectiveness; Engineering; Enteral; Enterovirus; Epidemic; Epidemiology; Etiology; Exhibits; experience; experimental study; fitness; fitness test; Future; Genetic; Genetic Recombination; Goals; Human poliovirus; Immunity; immunogenicity; Immunologics; improved; Inactivated Vaccines; Infection; invention; MicroRNAs; Modification; mouse model; Mucosal Immunity; Mus; Mutate; Mutation; Nature; nervous system disorder; Neurons; neurovirulence; novel sequencing technology; novel vaccines; Oral Poliovirus Vaccine; oral vaccine; Pathogenesis; Phase II Clinical Trials; Poliomyelitis; Poliovirus Vaccines; Polymerase; prevent; Public Health; respiratory virus; Safety; Serotyping; stem; Symptoms; Testing; Therapeutic; Time; tissue culture; tissue tropism; Tissues; transmission process; United States; vaccine candidate; vaccine development; Vaccines; Variant; Vertebral column; Virulence; Virulent; Virus
