Caltech Study Shows Promise for Broad-Spectrum Coronavirus Vaccine

In a groundbreaking study, Caltech researchers, in collaboration with scientists from Rockefeller University and the University of Washington, have demonstrated that a new vaccine candidate could offer protection against a wide range of coronaviruses, including SARS-CoV-2 and its variants. The research, conducted in the laboratory of Pamela Björkman, the David Baltimore Professor of Biology and Biological Engineering and a Merkin Institute Professor at Caltech, provides hope for a broader defense against future pandemics.

The study, published in the journal Cell on August 27, focused on a vaccine called mosaic-8. This innovative vaccine contains pieces of eight different sarbecoviruses, specifically regions of the viruses’ spike protein called receptor-binding domains (RBDs).

Researchers were particularly interested in how mosaic-8 would perform in individuals with pre-existing immunity to SARS-CoV-2. This question is crucial as nearly all Americans have been exposed to the virus through infection or vaccination, potentially leading to a phenomenon known as “original antigenic sin” (OAS).

“Current COVID-19 vaccines are not specifically designed to generate a broad antibody response that could offer better protection against variants or related viruses,” said Alexander Cohen, a postdoctoral scholar and co-first author of the study.

The team used both mouse and nonhuman primate models that had received prior COVID-19 vaccinations to mimic the immune status of most humans today. They immunized the animals with mRNA vaccines similar to the Pfizer and Moderna vaccines or with the ChAdOx1 vaccine from AstraZeneca before administering the mosaic-8 vaccine.

Encouragingly, the results showed that mosaic-8 elicited broadly protective antibodies in both previously exposed and immunologically naïve animals. The vaccine not only boosted existing antibodies but also drove the creation of new antibodies targeting regions specific to some of the seven animal sarbecovirus RBDs.

Jennifer Keeffe, senior research scientist and co-first author, explained the vaccine’s mechanism: “The goal is for our mosaic-8 vaccine to preferentially boost those kinds of antibodies so that the body makes more of them, providing broader protection.”

The study’s findings are particularly significant given the potential for future coronavirus outbreaks. Sarbecoviruses have caused two global health crises in the past two decades, highlighting the need for broad-spectrum protection.

Mosaic-8 works by targeting conserved regions of the virus’s spike protein, specifically the RBDs. By inducing antibodies against these shared features, the vaccine aims to protect against multiple sarbecoviruses and SARS-CoV-2 variants.

The research team’s next step is to confirm these promising results in human trials. Phase 1 clinical trials for the mosaic-8 vaccine are scheduled to begin in 2025, bringing hope for a more comprehensive defense against future coronavirus threats.

This California Institute of Technology study represents a significant advancement in vaccine development, potentially offering a solution to the challenge of viral mutations and emerging coronavirus strains. As the world continues to grapple with COVID-19, this research provides a glimpse of a more secure future.

The study was funded by Wellcome Leap, the National Institutes of Health, the Bill and Melinda Gates Foundation, the Coalition for Epidemic Preparedness Innovations, the Merkin Institute for Translational Research at California Institute of Technology, and the Stavros Niarchos Foundation Institute.