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，美国爆发了一种以前未知的神经系统疾病类似脊髓灰质炎的症状，后来被称为急性弛缓性脊髓炎 (AFM)，2016 年 AFM 病例每两年激增一次。从那时起，2018 年就引起了公共卫生官员的警惕，临床、免疫学和疾病方面的病例迅速积累。流行病学证据表明 EV-D68 是季节性 AFM 爆发的主要病原体在美国，EV-D68 是一种空气传播的呼吸道病毒，因此很难阻止其传播。目前尚无针对这种疾病的抗病毒治疗方法，这一事实凸显了开发一种治疗方法的重要性这种需求的紧迫性还源于疫苗开发需要时间，并且证实 EV-D68 为 AFM 病原体的证据表明，在此期间病例可能会再次增加 2020. 该项目的长期目标是生成 EV-D68 的活减毒变体并评估其我们的目标是设计一种 EV-D68 减毒活疫苗。候选者遵循我们最近开发的用于生成 nOPV2 的相同组合方法，改进的口服脊髓灰质炎疫苗源自 Sabin 2 型疫苗，目前正处于 II 期临床试验中。与 Sabin 具有相同的整体复制强度、疫苗适应性和免疫原性，但安全性明显更高因为它比 Sabin 的 OPV 具有更高的遗传稳定性，因此毒力回复率要低得多。