Yale norovirus vaccine candidate works in mice by reshaping viral RNA

Inside Yale laboratories, researchers changed the shape of norovirus's genetic material rather than simply targeting a protein on its surface. The resulting weakened virus candidate worked in mouse models, including immunocompromised mice, and triggered an immune response capable of neutralizing normal norovirus.

The reason lies in RNA, the molecule that carries the virus's genetic instructions. The Yale teams led by Anna Marie Pyle and Craig Wilen found that the norovirus genome is tightly folded, with structures that help it function. They looked for structural “hotspots,” then altered them by making small changes to the genome sequence. One successful change effectively “unzipped” part of the RNA containing the code for viral proteins, limiting the virus's ability to infect.

The need is large. Norovirus causes an estimated 685 million cases each year, and up to 200,000 deaths annually, including 50,000 child deaths, according to figures cited from the World Health Organization. There is currently no approved norovirus vaccine or treatment. The findings were published in Cell.

So what changes in practice? Not yet a shot for patients: the result is a laboratory-developed candidate tested in mice. But the method offers a route to designing weakened vaccines from an RNA virus's internal structures. The researchers say it could apply to other RNA viruses when their genetic sequence is known, including emerging pathogens.

The approach may also broaden the immune response. The Yale researchers say it can provide immunity against all proteins within a virus, unlike an mRNA vaccine that stimulates immunity to only one protein, such as the spike protein targeted by COVID-19 mRNA vaccines. That possibility remains a research direction, not a clinical result.