Fuller and Mullins Labs Collaborative Project Awarded a University of Washington Population Health Initiative COVID-19 Rapid Response Grant

The University of Washington Population Health Initiative announced the award of approximately $350,000 in COVID-19 rapid response grants to 21 different faculty-led teams. These teams are composed of individuals representing 10 different schools and colleges. Funding was partially matched by additional school, college and departmental funds, bringing the total value of these awards to roughly $820,000.

“A challenge of this magnitude requires us to draw upon the breadth of the university’s expertise to respond, and the range of innovative, collaborative project ideas that were quickly developed for this funding call was both impressive and truly inspiring,” shared Ali H. Mokdad, the university’s chief strategy officer for population health and professor of health metrics sciences. “We believe the 21 projects selected for funding are all well positioned to rapidly accelerate our understanding of, or approach to mitigating, the impacts of this pandemic, which is touching every aspect of our lives.”

The Population Health Initiative COVID-19 rapid response research grants are intended to rapidly accelerate, or jumpstart, novel research designed to better understand or mitigate the impact of COVID-19 on multiple facets of life.

 

Investigators
James I Mullins, Professor, Department of Microbiology
Deborah H. Fuller, Professor, Department of Microbiology
Jesse Erasmus, Postdoctoral Scholar, Department of Microbiology
Jim Fuller, Research Scientist, Department of Microbiology

Project abstract
Nearly all SARS-CoV-2 vaccines efforts are aimed at directing neutralizing antibodies (NAb) towards the viral Spike protein, intended to block the virus from entering cells through its normal receptor. However, these same Spike-directed NAb also have the potential to facilitate viral entry into immune cells through a different receptor, which can lead to Antibody Dependent Enhancement (ADE) of infection and disease. Antibodies from SARS virus infected persons induce ADE in cell culture but it is unclear if this occurs in people. Furthermore, we do not know how much the Spike gene might evolve before possibly returning with new waves of infections. Hence, new Spike vaccines may need to be developed each year the virus returns, as is needed to fight influenza.

We therefore need to rapidly develop alternative vaccines to stop COVID-19 pandemics from current and mutated strains that might circulate in future years. To this end, we designed vaccines to Focus Immune Responses on the Structural inTegrity (FIRST) of SARS-CoV-2 viral proteins. FIRST vaccines are intended to drive T cell and antibody responses that avoid antigenic features of each protein most likely to result in ADE while targeting features unlikely to change rapidly. Here, we will determine the expression of FIRST immunogens in cells and immune responses elicited in mice following delivery as RNA. Subsequently, lead immunogens will be tested with alternative delivery platforms to enable greater stability, lower manufacturing costs and needle free vaccination and a lead formulation selected to take forward into non-human primates and clinical trials.

Publication Date: 

Tuesday, May 5, 2020