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.

总结 2014年，美国爆发了一种以前未知的神经系统疾病， 脊髓灰质炎样症状，后来被称为急性弛缓性肌麻痹（AFM）。2016年AFM病例两年一度激增， 2018年，公共卫生官员感到震惊。从那时起，迅速积累的临床，免疫学， 流行病学证据指出EV-D 68是季节性AFM爆发的主要病原体 在美国. EV-D 68是一种空气传播的呼吸道病毒，因此很难预防其传播。这个和 事实上，目前还没有针对这种疾病的抗病毒治疗强调了开发一种 EV-D 68疫苗这一需求的紧迫性还源于疫苗开发需要时间， 证实EV-D 68为AFM病原体的证据表明， 2020. 该项目的长期目标是产生EV-D 68的减毒活变体，并评估它们的生物学特性。 作为潜在疫苗的安全性和有效性。我们的目标是设计EV-D 68减毒活疫苗， 候选人遵循相同的组合方法，我们最近开发了产生nOPV 2， 改良的口服脊髓灰质炎疫苗，来源于目前处于II期临床试验的Sabin 2型疫苗。nOPV 2展示 与Sabin的总体复制强度、接种者适应性和免疫原性相同，但安全性显著提高 因为它具有更大的遗传稳定性，因此比Sabin的OPV的毒力返强率低得多。