A Vaccine for Acute Flaccid Myelitis

急性弛缓性脊髓炎疫苗

基本信息

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
项目类别：
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&apos 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

项目摘要

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.

概括 2014年，美国爆发了以前未知的神经系统疾病类似脊髓灰质炎的符号后来称为急性松弛脊髓炎（AFM）。 2016年AFM病例的两年一度激增， 2018年令公共卫生官员感到震惊。从那时起，迅速积累了临床，免疫学和流行病学证据已指出EV-D68是季节性AFM暴发的主要结构药物在美国。 EV-D68是一种机载呼吸道病毒，因此很难防止其传播。这个和目前尚无抗病毒治疗的事实，强调了开发一个的重要性 EV-D68的疫苗。这种需求的紧迫性也从疫苗开发需要时间和证实EV-D68为AFM的病因的证据表明，案件可能会在 2020。该项目的长期目标是产生EV-D68的活体变体，并评估其安全性和有效性作为潜在疫苗。我们的目的是设计一种活衰减的EV-D68疫苗遵循我们最近开发的相同组合方法的候选人，以生成NOPV2，改善了目前在II期临床试验中的Sabin 2型疫苗的口服脊髓灰质炎疫苗。 NOPV2展品相同的总体复制强度，疫苗的适应性和萨宾的免疫原性，但明显更安全因为它具有更大的遗传稳定性，因此与Sabin的OPV相比，与病毒相反的速率要低得多。