Published: March 25, 2021 By

As millions of people around the world receive vaccines to halt the spread of COVID-19, mutated variants of the virus continue to appear, challenging the efficacy of mass vaccination programs and social distancing.

New research from the Sprenger and Whitehead groups aims to identify and map common mutations in “Spike” proteins—the proteins that allow the virus to enter and infect cells. This  would provide researchers with a roadmap to anticipate and counteract the development of future SARS-CoV-2 strains with effective vaccines and vaccine boosters.

The collaborative research combined the Sprenger group’s expertise in computational methods to study how antibodies interact with viral proteins with the unique technological capabilities of the Whitehead group.

“We identified common Spike mutations for certain antibodies that are elicited during natural infection from the virus,” said Associate Professor Timothy Whitehead. “These mutations may emerge in lineages after population vaccination, and a prospective knowledge of these mutations may allow us to develop better vaccine boosters and therapies against SARS-CoV-2.”

The researchers utilized a genetically engineered strain of yeast, which expressed portions of the viral Spike proteins along its surface. They created mutant variations of the Spike proteins and studied their ability to go unrecognized by antibodies—essentially modeling the potential mutations of SARS-CoV-2.

Irene Francino Urdaniz
Irene Francino Urdaniz

"Molecular simulations can provide unique insight into the mechanisms by which the identified Spike mutations allow SARS-CoV-2 to escape pressure by the immune system,” said Assistant Professor Kayla Sprenger. “We observed common escape mechanisms from multiple neutralizing antibodies with the same germline gene origins, which may have important implications for future SARS-CoV-2 immunotherapeutics."

Whitehead credits one of his graduate students, Irene Francino Urdaniz, with leading the effort in his lab.

“When the pandemic started, we saw the opportunity to apply techniques mastered by the Whitehead lab to make a contribution,” Francino Urdaniz said.

“We set up a system to test how well antibodies neutralize SARS-CoV-2 by displaying the S RBD on the yeast cell’s surface. Early in the process, we had the extraordinary opportunity to collaborate with Brandon Dekosky’s lab and the Vaccine Research Center to characterize a newly discovered neutralizing antibody with our platform.”

“Francino Urdaniz developed the genetically engineered yeast strain and discovered how to screen for mutations on the Spike protein that result in loss of antibody efficacy,” Whitehead said. “She is a Balsells fellow and represents the fantastic students we are able to recruit from the best universities in Europe.”

Other institutions involved in the work include University of Kansas, The Scripps Research Institute, the International AIDS Vaccine Initiative, Columbia University and the NIH Vaccine Research Center.