A Vaccine for Acute Flaccid Myelitis
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Principal Investigator: Raul Andino Organization: ALEPH THERAPEUTICS, INC. Fiscal Year: 2020 Award: $250,215 Funding agency: National Institute of Allergy and Infectious Diseases SUMMARY 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 Sabin’s OPV. Terms: <3-D><3-Dimensional><3D><5' Untranslated Regions><5'UTR><Acute Poliomyelitis><Antiviral Agents><Antiviral Drugs><Antivirals><Attenuated><Attenuated Live Virus Vaccine><Attenuated Vaccines><Biologic Models><Biological><Biological Models><Body Tissues><Capsid><Capsid Proteins><Causality><Chimera><Chimera organism><Clinical><Coat Proteins><Communities><DNA Recombination><Development><Disease><Disease Outbreaks><Disorder><Effectiveness><Engineering><Enteral><Enteric><Enterovirus><Enterovirus Infections><Epidemic><Epidemiology><Etiology><Exhibits><Future><Genetic><Genetic Alteration><Genetic Change><Genetic Recombination><Genetic defect><Goals><Human poliovirus><Immunity><Immunochemical Immunologic><Immunologic><Immunological><Immunologically><Immunologics><Inactivated Vaccines><Inactivated Virus Vaccine><Infection><Killed Vaccines><Live-attenuated Vaccine><Mice><Mice Mammals><Micro RNA><MicroRNAs><Model System><Modification><Mucosal Immunity><Murine><Mus><Mutate><Mutation><Nature><Nerve Cells><Nerve Unit><Nervous System Diseases><Neural Cell><Neurocyte><Neurologic Disorders><Neurological Disorders><Neurons><Oral Polio Vaccine><Oral Poliovirus Vaccine><Outbreaks><Pathogenesis><Phase 2 Clinical Trials><Phase II Clinical Trials><Polio><Polio Vaccine><Polio Virus><Poliomyelitis><Poliovirus><Poliovirus Vaccines><Polymerase><Public Health><Recombination><Sabin Vaccine><Safety><Salk Vaccine><Serotyping><Spinal Column><Spine><Symptoms><Testing><Therapeutic><Time><Tissues><Transmission><United States><Vaccines><Variant><Variation><Vertebral column><Viral Coat Proteins><Viral Outer Coat Protein><Virulence><Virulent><Virus><acute flaccid myelitis><anti-viral agents><anti-viral drugs><anti-virals><attenuation><backbone><causation><combinatorial><design><designing><develop a vaccine><development of a vaccine><developmental><disease causation><emerging sequencing technology><epidemiologic><epidemiological><experience><experiment><experimental research><experimental study><fitness><fitness test><genome mutation><immunogenicity><improved><invention><live vaccine><mRNA Leader Sequences><miRNA><miRNAs><mouse model><murine model><nervous system disorder><neurological disease><neuronal><neurovirulence><new sequencing technology><new vaccines><next generation vaccines><novel sequencing technology><novel vaccines><oral vaccine><phase II protocol><poliomyelitis vaccine><poliomyelitis virus><prevent><preventing><respiratory virus><stem><three dimensional><tissue culture><tissue tropism><transmission process><vaccine candidate><vaccine development><vaccine formulation>