Novel vaccine strategy protects mice from COVID-19 and 4 related coronaviruses

SARS-CoV-2
An Osaka University team targeted the core of the coronavirus spike protein's receptor-binding domain in an effort to develop a universal vaccine. (libre de droit/iStock/Getty Images Plus)

The three marketed COVID-19 shots have validated the effectiveness of two vaccination technologies, mRNA and viral vector delivery. But the vaccines—from Pfizer/BioNTech, Moderna and Johnson & Johnson—only protect against SARS-CoV-2, the coronavirus that sparked the pandemic. So a team of researchers in Japan set out to develop a universal coronavirus vaccine in the hopes of preventing future pandemics.

Scientists at Osaka University engineered antibodies that prevented SARS-CoV-2 from infecting healthy cells in mice, they reported in the Journal of Experimental Medicine. They were also effective against SARS-CoV-1, which caused a small outbreak in the early 2000s, and three coronaviruses found in pangolins and bats, they said.

The experimental vaccination approach exploits the biology of the SARS-CoV-2 spike protein, which shuttles the virus into human cells by binding to a cell surface receptor called ACE2. The spike protein’s receptor-binding domain has a “head” region that facilitates that binding as well as a “core” region. While the head of each type of coronavirus is distinctive, the core regions are virtually identical.

Problem is, when people are exposed to SARS-CoV-2 by infection or vaccination, they produce antibodies that mostly recognize the head, but not the core of the spike protein. So to make a universal coronavirus vaccine, the Osaka University scientists had to figure out how to target the protein’s core.

They solved the problem by genetically engineering the receptor-binding domain of the spike protein and then covering the head region with extra sugar molecules. The sugar prevented the immune system from recognizing the head region, the researchers explained in a statement. That prompted the immune system to produce antibodies that mostly recognized the core region instead.

They immunized mice with the engineered receptor-binding domain and tracked the production of antibodies that resulted. The proportion of antibodies that recognized the core region was much higher than that of antibodies specific to the head region, they reported. And the core-specific antibodies prevented infection by the five coronaviruses tested.

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Osaka University’s strategy is among many proposals for improving the scientific approach to virus outbreaks. Last year, for example, startup Osivax raised $33.8 million to fund its research into universal flu and coronavirus vaccines. It’s approach also revolves around targeting regions of viruses that are conserved rather than those that can change or mutate.

Tomohiro Kurosaki, a professor at Osaka University and co-author of the new study, said the vaccination strategy developed by his team will need more work before it can be tried in people, but he believes it’s an effort worth pursuing.

“Given that prior coronavirus epidemics such as SARS-CoV-1 and MERS-CoV have occurred due to zoonotic coronaviruses crossing the species barrier, the potential for the emergence of similar viruses in the future poses a significant threat to global public health, even in the face of effective vaccines for current viruses,” he said.