PI: William Wagner
Co-PI: John Alcorn, Stephen Badylak, Louis Falo, William Federspiel, Neeraj Gandhi, Eric Lagasse, Steven Little, Alan Wells, and Cecilia Yates
Title: Therapies for COVID-related Disease and Technology Development
Description: Since December 2020, the FDA (Federal Drug Administration) emergency use authorization of two vaccines directed against SARS-CoV-2 (COVID 19 or Coronavirus) has changed the trajectory and future of personal and public health management of COVID-19. While these vaccines show success rates as high as 95% in preventing severe COVID-19 adverse events, these vaccine studies did not investigate the efficacy of these vaccines in the context of a patient receiving immunomodulatory therapies for either COVID-19 or a separate comorbidity. The Badylak laboratory at the University of Pittsburgh completed a pilot study investigating the efficacy of recently characterized, immunomodulatory matrix-bound nanovesicles (MBV) in treatment of viral-induced pulmonary infection and inflammation. In this study, preliminary results demonstrate a significant reduction in overall lung inflammation and promotion of a systemic immune response that is both anti-viral and anti-inflammatory in properties. While promising, the observed immunomodulatory effect of MBV has an unknown effect on the well-described and predictable vaccine-driven immune response. Therefore, with more patients becoming vaccinated against COVID-19 every day, it is of immense importance to pursue investigation into the effect of MBV on a normal vaccine response. The translational viability of MBV therapy for COVID-19 will only be successful if the patient’s ability to mount a physiologic vaccine response is preserved throughout and following treatment.
In this project, we will use funds to investigate two central questions: 1.) Can immunomodulatory MBV be administered by intravenous (IV, systemic) injection to treat COVID-19 mediated lung infection, and 2.) does administration of MBV have any adverse effects on the host ability to mount an effective (virus neutralizing) immune response? Using murine models of COVID-19 and H1N1, we will investigate the therapeutic potential of MBV in these two examples of viral-mediated lung inflammation. Since the COVID-19 vaccines are not available at the present moment for research use, we will use the influenza vaccine as a model response. Since vaccine responses are well-conserved across the type of vaccine, we will be able to extrapolate results from this study and apply them to our understanding of the COVID-19 vaccine.
To address question 1, we will use the transgenic ACE2 (angiotensin-converting enzyme expressing mice) (wild-type mice cannot be infected with COVID-19 since they lack the ACE2 receptor) to study the efficacy of MBV in mediating COVID-19 lung inflammation. To address question 2, we will use wildtype mice. To study the effect of MBV on the normal vaccine response, animals will be treated with MBV before and during vaccination with the H1N1 (influenza A virus subtype) vaccine. After the vaccine period, animals will then be infected with live H1N1 and survival and lung inflammation will be used as metrics to determine safety and compatibility of MBV with vaccines.
Source: Pennsylvania Department of Human Services (DHS)
Term: 2 Years
Amount: $4 million