Coronavirus Pathogenesis and Broadly Protective Vaccine Development

冠状病毒发病机制和广泛保护性疫苗的开发

• 批准号: 10692225
• 负责人: Matthew Memoli
• 金额: $ 99.16万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10692225
• 关键词: 2019-nCoV; Address; Affect; Antibodies; Antibody titer measurement; Biological; COVID-19 pandemic; Clinical; Clinical Trials; Collaborations; Communities; Contracts; Coronavirus; Data; Disease; Economics; Enrollment; Epidemiology; Future; Gene Expression Profiling; General Population; Immune response; Immunity; In Vitro; Individual; Infection; Knowledge; Lead; Learning; Modeling; Morbidity - disease rate; National Center for Advancing Translational Sciences; Participant; Pathogenesis; Pathology; Persons; Play; Population; Prevalence; Public Health; Publishing; Rare Diseases; Recording of previous events; Role; SARS-CoV-2 infection; SARS-CoV-2 pathogenesis; Sampling; Seeds; Severities; Surveys; Time; Vaccines; Variant; Viral; Virus; Work; betacoronavirus; betacoronavirus vaccine; coronavirus vaccine; design; healthy volunteer; insight; mortality; pandemic disease; phase I trial; pre-clinical; response; seroconversion; serosurvey; vaccine development; vaccine evaluation

The SARS-COV-2 virus has had a major impact on morbidity and mortality worldwide, as well as having devastating global economic and societal impact. The overall impact cannot be quantified, some of which is due to the worldwide public health response and not the virus itself. Knowledge of the antibody levels present in a population could offer great insights into current and future response efforts. We need far more information to fully understand what impact immunity will have on the spread and severity of this and future pandemic viruses. This knowledge could change how we handle the next stages of this pandemic, the post pandemic period, and prepare for future pandemics. Therefore, we completed a nationwide serosurvey to enroll a 10,000 person representative sample of the US population to determine how many individuals have been exposed/infected with SARS-CoV-2 during the initial stages of the pandemic. The first portion of this study was published offering insight into the early portion of the pandemic and the epidemiology and immune response early on. We then followed these individuals longitudinally and retested them at 6 months and 12 months to look for seroconversion and history of documented infection. This allows us to assess correlates of protection and the trajectory of antibody titers over time. The data yielded from this study, in conjunction with other similar studies can better guide the decisions that are made as this pandemic continues. We hope to publish these data in the coming year offering even further insight into this pandemic. In addition to our nationwide serosurvey we have also initiated a project to study individuals with rare diseases. This study in collaboration with the NCATS RDCRN evaluated how the COVID19 pandemic has affected individuals living with over 500 different rare diseases. The RDCRN has initiated an online survey and we initiated biological sampling to allow us to better identify the level of exposure and immunity in this niche community. We expect to publish these data over the next year and the data from this study will allow us to better understand how we can better address the pandemic needs of this community that is often overlooked. We have initiated work in collaboration with Jeff Taubenberger's VPES to develop a broadly protective, universal beta-coronavirus vaccine. We are playing a lead role in the design and manufacture of these vaccines. Once the VPES completes preclinical work and we are able to complete GMP manufacturing, we hope to begin with phase I trials. We also have collaborated with the VPES to investigate various aspects of SARS-COV2 pathogenesis including a large scale pathology study of those with severe disease, gene expression analysis, and in vitro studies of viral variants. Lastly, we are working on developing challenge models for beta-coronaviruses that may be used to study pathogenesis as well as testing vaccines. We currently have made a seed virus from an OC43 beta-coronavirus and have a contract in place to initiate GMP manufacture.

SARS-COV-2病毒对全世界的发病率和死亡率产生了重大影响，并对全球经济和社会产生了破坏性影响。 总体影响无法量化，其中一些是由于全球公共卫生应对措施，而不是病毒本身。 了解人群中存在的抗体水平可以为当前和未来的应对工作提供很好的见解。我们需要更多的信息来充分了解免疫对这次和未来大流行病毒的传播和严重性的影响。 这些知识可能会改变我们如何处理这场大流行的下一个阶段，大流行后时期，以及为未来的大流行做准备。 因此，我们完成了一项全国性的血清调查，招募了10，000人的美国人口代表性样本，以确定有多少人在大流行的初始阶段暴露/感染了SARS-CoV-2。 本研究的第一部分发表，提供了对大流行的早期部分和早期流行病学和免疫反应的深入了解，然后我们纵向跟踪这些个体，并在6个月和12个月时重新测试，以寻找血清转换和记录的感染史。 这使我们能够评估保护的相关性和抗体滴度随时间的轨迹。 从这项研究中获得的数据，与其他类似的研究相结合，可以更好地指导决策，因为这一流行病仍在继续。 我们希望在未来一年公布这些数据，以进一步了解这一流行病。 除了我们的全国性血清调查外，我们还启动了一个研究罕见疾病患者的项目。 这项与NCATS RDCRN合作的研究评估了COVID 19大流行如何影响患有500多种不同罕见疾病的个体。 RDCRN已经启动了一项在线调查，我们启动了生物采样，以使我们能够更好地确定这个利基社区的暴露水平和免疫力。 我们预计将在明年公布这些数据，这项研究的数据将使我们更好地了解我们如何更好地解决这个经常被忽视的社区的流行病需求。 我们已经开始与Jeff Taubenberger的VPES合作开发一种具有广泛保护性的通用β冠状病毒疫苗。 我们在这些疫苗的设计和生产中发挥着主导作用。 一旦VPES完成临床前工作，我们能够完成GMP生产，我们希望开始I期试验。 我们还与VPES合作研究SARS-COV 2发病机制的各个方面，包括对严重疾病患者的大规模病理学研究，基因表达分析和病毒变体的体外研究。 最后，我们正在开发β-冠状病毒的挑战模型，可用于研究发病机制和测试疫苗。 我们目前已经从OC 43 β-冠状病毒中制备了种子病毒，并签订了启动GMP生产的合同。