Coronavirus Pathogenesis and Broadly Protective Vaccine Development

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毁灭性的影响。总体影响无法量化，其中一些是由于全球公共卫生反应，而不是病毒本身。对人群中存在的抗体水平的了解可以为当前和未来的应对努力提供很好的见解。我们需要更多的信息来充分了解免疫将对这次和未来大流行病毒的传播和严重程度产生什么影响。这一知识可能改变我们处理这场大流行的下一阶段、大流行后时期的方式，并为未来的大流行做好准备。因此，我们完成了一项全国性的血清调查，招募了10,000名具有代表性的美国人口样本，以确定有多少人在疫情初期接触/感染了SARS-CoV-2。这项研究的第一部分已发表，提供了对大流行的早期部分以及流行病学和免疫反应的早期洞察。然后，我们对这些患者进行了纵向跟踪，并在6个月和12个月时对他们进行了重新测试，以寻找血清转换和有记录的感染史。这使我们能够评估保护的相关性和抗体滴度随时间的变化轨迹。这项研究结合其他类似研究得出的数据可以更好地指导随着这场大流行的继续而做出的决定。我们希望在来年公布这些数据，进一步深入了解这场大流行。 除了我们在全国范围内的血清调查外，我们还发起了一个研究患有罕见疾病的个人的项目。这项研究与NCATS RDCRN合作，评估了COVID19大流行如何影响患有500多种不同罕见疾病的个人。RDCRN已经启动了一项在线调查，我们也启动了生物采样，以使我们能够更好地确定这个利基社区的暴露和免疫水平。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能够更好地了解如何更好地满足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，开发一种广泛保护、通用的贝塔冠状病毒疫苗。我们在这些疫苗的设计和制造中发挥着主导作用。一旦VPES完成临床前工作，我们能够完成GMP生产，我们希望开始第一阶段的试验。 我们还与VPES合作研究SARS-COV2致病机理的各个方面，包括对重症患者的大规模病理学研究、基因表达分析以及病毒变异的体外研究。 最后，我们正在致力于开发针对贝塔冠状病毒的挑战模型，该模型可用于研究发病机制以及测试疫苗。我们目前已经从OC43β冠状病毒中制造了一种种子病毒，并签订了启动GMP生产的合同。

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.