Coronavirus Pathogenesis and Broadly Protective Vaccine Development

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The newly emerged SARS-COV-2 virus currently causing a pandemic 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 disease and the true extent of the disease. That information could help us focus on those at risk rather than continuing large-scale quarantines/social distancing of the entire population. This knowledge could also change how we handle the next stages of this pandemic, prepare for a possible second wave, and could influence our response to future pandemics. Therefore, we initiated 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. We will then follow these individuals longitudinally and retest them at 6 months and 12 months to look for seroconversion and history of documented infection. This will allow for assessment of correlates of protection and trajectory of antibody titers over time. The data yielded from this study, in conjunction with other similar studies may be available rapidly in the next few months, can better guide the decisions that are made as this pandemic continues. We hypothesize that more people likely have been infected or exposed to this virus than is currently documented by confirmed infections. It is likely that a significant number of individuals already have antibodies to the virus due to asymptomatic or undiagnosed infections. 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, will evaluate how the COVID19 pandemic has affected individuals living with over 500 different rare diseases. The RDCRN has initiated an online survey and we are initiating biological sampling to allow us to better identify the level of exposure and immunity in this niche community. We expect that over the next year this longitudinal 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 Taubenbergers VPES to develop a broadly protective, universal beta-coronavirus vaccine. We are playing a lead role in the design and manufacture of these vaccines. In this project we are taking various representative beta-coronaviruses, including SARS-CoV-2 from the four distinct clades of beta-coronaviruses and making inactivated versions of the viruses. We are also pursuing a VLP version of each as well. Once the VPES completes preclinical work and we are able to complete GMP manufacturing later this year, we hope to begin with phase I trials. 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 hope to initiate GMP manufacture. We are also leading the efforts to create a SARS-CoV-2 challenge model protocol and are working closely with DMID in the manufacture of a GMP challenge virus.