A Vaccine for Acute Flaccid Myelitis

急性弛缓性脊髓炎疫苗

• 批准号: 10080611
• 负责人: Raul Andino
• 金额: $ 25.02万
• 依托单位: ALEPH THERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-10 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10080611
• 关键词: 3-Dimensional; 5' Untranslated Regions; Antiviral Agents; Attenuated; Attenuated Live Virus Vaccine; Attenuated Vaccines; Biological; Biological Models; Capsid; Capsid Proteins; Chimera organism; Clinical; Communities; Development; Disease; Disease Outbreaks; Effectiveness; Engineering; Enteral; Enterovirus; Epidemic; Epidemiology; Etiology; Exhibits; Future; Genetic; Genetic Recombination; Goals; Human poliovirus; Immunity; Immunologics; Inactivated Vaccines; Infection; MicroRNAs; Modification; Mucosal Immunity; Mus; Mutate; Mutation; Nature; Neurons; Oral Poliovirus Vaccine; Pathogenesis; Phase II Clinical Trials; Poliomyelitis; Poliovirus Vaccines; Polymerase; Public Health; Safety; Serotyping; Symptoms; Testing; Therapeutic; Time; Tissues; United States; Vaccines; Variant; Vertebral column; Virulence; Virulent; Virus; acute flaccid myelitis; attenuation; combinatorial; design; experience; experimental study; fitness; fitness test; immunogenicity; improved; invention; mouse model; nervous system disorder; neurovirulence; novel sequencing technology; novel vaccines; oral vaccine; prevent; respiratory virus; stem; tissue culture; tissue tropism; transmission process; vaccine candidate; vaccine development

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.

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