Scientists overcome key barrier to self-amplifying vaccines

Scientists at Queen Mary University of London have found a way to overcome cells’ natural defenses against self-amplifying mRNA vaccines, allowing the cells to produce significantly more of the target protein. The findings are published in Nature Communications.

mRNA-based vaccines were central to getting us out of the COVID-19 pandemic. Unlike conventional vaccines, which use a low dose of a virus to build immunity, RNA vaccines tell your cells to produce a protein that teaches your body how to fight the virus.

Since then, scientists have been working on self-amplifying mRNA (saRNA) vaccines, which replicate within host cells. These next-generation vaccines could provide longer-lasting protection at lower doses, meaning they could be rolled out more widely and faster than previously imaginable.

The benefits go beyond pandemic protection. saRNA vaccines hold great promise as a novel strategy in gene therapy, cancer immunotherapy and protein replacement therapies.

The barrier to saRNA vaccines lies within the technology itself.

As saRNA replicates, it generates double-stranded RNA (dsRNA), which triggers cells’ antiviral defenses. This makes the saRNA less stable, less able to replicate and less able to instruct cells to produce the protein that trains the immune system. It’s a major flaw limiting how effective an saRNA vaccine can be.

Dr. Pierre Maillard and Dr. Raul Yusef Sanchez David, scientists at Queen Mary University of London’s Blizard Institute, found that adding NoV B2 helps overcome this problem. The protein is known to suppress RNA interference, one of the cell’s natural defenses against this double-stranded RNA.

By reducing the extent to which cells restrict the saRNA, NoV B2 allows it to produce far more of the intended protein in both stem cells and regular cells. Crucially, it does so without undermining saRNA’s ability to stimulate the immune system.

Maillard, senior lecturer in antiviral immunity at Queen Mary University of London, said, “Our findings identify a strategy to overcome a fundamental barrier limiting self-amplifying vaccines. If this translates successfully in vivo, it could open new possibilities for vaccine design as well as for gene therapies and cancer treatment.”

A new generation of vaccines

The team is now working with Queen Mary Innovation, the university’s technology transfer company, to find a commercial partner to help develop the technique for clinical use.

By boosting how much protein saRNA can produce in the lab, the innovation opens new possibilities in gene therapy, cancer immunotherapy and protein replacement therapies. If translated successfully, this technology could make gene therapy safer and more affordable, make cancer vaccines more potent, and turn protein replacement therapy from a process of repeated infusions into one in which the patient’s body generates its own medicine.

The advance comes amid growing debate over funding for mRNA-based research following a U.S. announcement of $500 million in cuts to mRNA vaccine research, a decision that sparked widespread concern in the global scientific and public health communities.

Maillard and Sanchez David’s discoveries at Queen Mary demonstrate the continued strength of the United Kingdom as a place to invest in research and innovation.

Who’s behind this story?

Sadie Harley

BSc Life Sciences & Ecology. Microbiology lab background with pharmaceutical news experience in oil, gas, and renewable industries.

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Robert Egan

Bachelor’s in mathematical biology, Master’s in creative writing. Well-traveled with unique perspectives on science and language.

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