The goal of this proposal is to increase the understanding of SARS-CoV-2 transmission amongst naïve, recovering or vaccinated individuals. The current COVID pandemic is a stark illustration of the global interdependence between people and other animals. Resumption of normal societal function in the current COVID crisis will require immunity to SARS-CoV-2 either through natural means or through vaccination on a global scale. The rate at which unexposed people (currently most of the human population) become infected or ill is affected by many factors, including the potential for partial immunity (following natural exposure or vaccination) and subsequent reinfection. Use of naturally-occurring related coronaviruses in other animals to emulate this process is a novel and practical approach, and that is the goal of this proposal here. Rat sialodacryoadenitis virus (SADV) has transmission features that closely approximate those of SARS-CoV-2 and a similarly rapid disease course. Animals can be partly protected using another rat coronavirus (RCV) thus emulating vaccination. These characteristics allow researchers to perform rapid transmission studies to produce real transmission data that can be used in predictive models. Broader impacts include that these models can more accurately guide regional preventive measures such as social distancing, to minimize SARS-CoV-2 spread. An additional broader impact is the training of several junior scientists, and an all-female set of investigators, broadening participation of science.
This proposal will use sialodacryoadenitis virus (SDAV), a rat coronavirus with transmission features that closely approximate those of SARS-Cov2, to generate in vivo transmission estimates in rats informing a data-driven core SEIRS (Susceptible - Exposed ? Infected ? Recovered - Susceptible) simulation model. In Aim 1, rates of infection and recovery will be determined in susceptible (naïve) rats following exposure to SDAV. Thus, this models the current global dynamic of the SARS-Cov-2 pandemic. In Aims 2 and 3, the rates of infection and recovery will be determined in convalescing rats from aim 1 who receive a second near-term or long-term exposure to SDAV, respectively. This assesses the potential for individuals with recent naturally-acquired immunity to shed virus and models the near-term dynamics of SARS Cov-2 (aim 2), and the potential for individuals with waning naturally acquired immunity to shed virus and models the near to long-term dynamic of SARS CoV-2 (aim 3). Aim 4 will determine rates of infection and recovery in rats vaccinated with a related rat coronavirus (RCV), a vaccination known to provide partial immunity against SDAV, following exposure to SDAV shedding rats. This aim assesses the potential for individuals developing variable vaccine acquired immunity to shed virus and models the long-term dynamic of SARS CoV-2. Estimates obtained in Aims 1-4 will be used to construct a core mathematical model in NumerusMB. This will allow simulation of complex scenarios testing the effects of vaccination and social mixing on the susceptible population. This RAPID award is made by the Physiological and Structural Systems Cluster in the BIO Division of Integrative Organismal Systems, using funds from the Coronavirus Aid, Relief, and Economic Security (CARES) Act.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
