La Jolla Institute scientists team up with Brigham and Women’s Hospital to guide the development of vaccines against the coronavirus family
The COVID-19 pandemic revealed how easily the family of coronaviruses can mutate to become more transmissible and deadly. A “pan”-coronavirus vaccine would ideally give humanity protection against future outbreaks of any coronavirus.
“Rather than having to constantly launch new vaccines,” says La Jolla Institute for Immunology (LJI) Professor and President Erica Ollmann Saphire, Ph.D. “We need a single vaccine that’s going to protect against SARS-CoV-2 variants and whatever coronavirus emerges next.”
Now Saphire and her team have received more than $2.6 million in funding from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, to help develop a pan-coronavirus vaccine that could be effective for years to come. The three-year project builds on the Saphire Lab’s success in designing accurate models of key viral protein structures.
Saphire’s new investigation is a key part of a Brigham and Women’s Hospital-led project, “Discovering Durable Pan-Coronavirus Immunity,” spearheaded by Duane Wesemann, M.D., Ph.D., associate professor of Medicine at Harvard Medical School and associate physician at Brigham and Women’s Hospital. The overall project has been granted more than $11.8 million over three years and includes collaborators at Massachusetts General Hospital.
The team is focused on finding the sites on the SARS-CoV-2 structure that could also be targeted on other types of coronaviruses. These “conserved” sites are often key features on the virus’ spike protein base that are unlikely to mutate as the overall virus changes.
“Our multi-disciplinary team will conduct research to identify pieces of SARS-CoV-2 that may be conserved across other coronaviruses, and we will study the effectiveness of antibodies and T cell activity against these regions,” says Wesemann.
Work in the Saphire Lab will be spearheaded by LJI Postdoctoral Fellow Eduardo Olmedillas, Ph.D., a structural virologist behind the development of VFLIP, a more stable, more accurate version of the SARS-CoV-2 “spike” protein, compared with the early spike models used to develop the first generation of COVID-19 vaccines.
VFLIP is a valuable tool for identifying conserved sites because it is coated with the same carbohydrate molecules that cover the real SARS-CoV-2 spike protein. Saphire compares exposing immune cells to the VFLIP structure to showing them a high-resolution mugshot of SARS-CoV-2. Importantly, VFLIP is a hardy structure and can hold its shape even after weeks at room temperature—making it an ideal tool for COVID-19 studies around the world.
“Stabilizing these parts of spike helps us elicit more protective, broadly reactive antibodies,” says Saphire, who also leads the Coronavirus Immunotherapy Consortium (CoVIC).
“The stability of VFLIP, its robust production and its ability to elicit a potent, long-lasting antibody response capable of neutralizing the infectivity of different variants of SARS-CoV-2 make this immunogen an excellent tool for the design of novel pan-coronavirus vaccines,” says Olmedillas. “The biophysical characteristics of VFLIP allow its further study in vaccine platforms such mRNA and nanoparticle-based vaccines, which broadens the possibilities of designing more broad and potent pan-coronavirus vaccines.”
Wesemann’s team will also use animal models to test immunization strategies, determining the optimal parameters for dosing, delivery and other factors that may influence a broad response.
The award is funded by NIAID’s Division of Microbiology and Infectious Diseases and its Division of Allergy, Immunology and Transplantation through the Emergency Awards Notice of Special Interest (NOSI) on Pan-Coronavirus Vaccine Development Program Projects. The awards are intended to foster research on vaccines that can confer broad protective immunity against coronaviruses, such as Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV). The award to Saphire is NIAID grant number 1P01AI165072-01, Sub-Project ID 6660.
