This winter, norovirus outbreaks surged across the U.S., with cases nearly doubling from last year, according to the CDC. Schools, cruise ships, nursing homes and healthcare facilities saw widespread illness, underscoring the urgent need for a norovirus vaccine.
Each year, norovirus causes 685 million infections worldwide and is the leading cause of foodborne illness in the U.S., responsible for 21 million cases annually. Despite its massive impact, there is still no approved vaccine—but recent advancements suggest that this could change.
Moderna’s mRNA-based norovirus vaccine, mRNA-1403, entered Phase 3 clinical trials in 2024, aiming to provide broad protection. However, in February 2025, the FDA placed the trial on hold following a reported case of Guillain-Barré syndrome. Meanwhile, other vaccine candidates, including Vaxart’s oral tablet vaccine, continue progressing through clinical trials.
So, how close are we to a breakthrough? Let’s explore the latest research, challenges, and the road ahead for norovirus vaccine development.
The Case for a Norovirus Vaccine
A Widespread and Costly Virus
Norovirus is a major driver of gastroenteritis worldwide, linked to200,000 deaths annually—particularly in low-income countries. Beyond the health burden, norovirus infections cost an estimated $60 billion globally each yearin healthcare expenses and lost productivity.
Who’s Most at Risk?
While anyone can contract norovirus, certain populations face a higher risk of severe illness, prolonged symptoms, and complications.
- Young children – Infants and toddlers are particularly vulnerable due to their developing immune systems and higher risk of dehydration.
- Older adults – Individuals over 65 are more likely to experience severe dehydration, extended illness duration, and complications due to age-related immune decline (1).
- Immunocompromised individuals – People with weakened immune systems, including cancer patients, transplant recipients, and those with chronic illnesses, may struggle to clear norovirus from their bodies, leading to prolonged or recurrent infections (2).
Why Norovirus is Hard to Control
Norovirus spreads quickly and efficiently, and is difficult to control due to several factors:
- High Contagiousness: The virus can be transmitted through food, water, surfaces and direct contact.
- Environmental Resiliency: Norovirus can survive on surfaces and in water for days or even weeks, and is resilient to standard cleaning products.
- Lack of Specific Treatment: Currently, there is no specific antiviral treatment for norovirus; management primarily involves supportive care to alleviate symptoms.
Given these challenges, the development of an effective norovirus vaccine is crucial to reducing the global burden of this pervasive pathogen.
Current Vaccine Candidates
Moderna’s mRNA-1403 Vaccine
Moderna has been at the forefront of norovirus vaccine development with mRNA-1403, a trivalent vaccine designed to protect against multiple strains. The Phase 3 Nova 301 trial, launched in September 2024, sought to enroll 25,000 participants globally.
However, in February 2025, the FDA paused the trial due to a Guillain-Barré syndrome case—a setback that raises questions about next steps. While this type of setback is not uncommon in vaccine development, it’s unclear how long the trial will remain on hold or whether adjustments will be needed before it can move forward.
Vaxart’s Oral Norovirus Vaccine
Another promising candidate comes from Vaxart, a company developing an oral table vaccine. Unlike traditional injectable vaccines, Vaxart’s approach is designed to stimulate mucosal immunity, which could be the key to preventing norovirus infections at their point of entry.
Their bivalent vaccine, targeting GI and GII norovirus genogroups, showed strong immune responses and reduced viral shedding in Phase 2 trials. While promising, Vaxart has yet to begin a Phase 3 trial, meaning approval is still years away.
Other Vaccine Approaches
Beyond Moderna and Vaxart, smaller biotech firms and research institutions are exploring virus-like particle (VLP) vaccines and combination vaccines that integrate norovirus antigens with other gastroenteric pathogens like rotavirus.
One novel approach from Washington University School of Medicine in St. Louis involves engineering a harmless strain of rotavirus to express a norovirus protein, effectively stimulating an immune response against both viruses. In preclinical studies, this experimental vaccine induced the production of neutralizing antibodies against both norovirus and rotavirus in mice, suggesting potential for a broad-spectrum solution (3).
How Close Are We to a Vaccine?
Despite these advancements, norovirus vaccine development faces various challenges:
- Regulatory hurdles: The FDA pause on Moderna’s trial highlights safety concerns that could delay approval.
- Genetic diversity: Norovirus mutates frequently, requiring that a vaccine provide broad-spectrum protection.
- Short-lived immunity: Past research suggests norovirus immunity may not last long, complicating vaccine design.
While Moderna and Vaxart’s candidates are among the most advanced, no norovirus vaccine has been submitted for FDA or EMA approval–meaning widespread availability is still a distant goal.
Conclusion
Norovirus remains a serious global health issue, responsible for millions of infections and billions in economic costs each year. While vaccine development has accelerated in recent years, scientific and regulatory challenges persist.
The earliest possible approval for a norovirus vaccine is still years away, depending on the outcome of ongoing trials. Until then, preventative measures remain our best defense–including frequent handwashing, proper food handling, and thorough surface disinfection.
A norovirus vaccine may be on the horizon, but until an approved vaccine reaches the public, staying vigilant is our best strategy against one of the world’s most persistent and contagious viruses.
References
- Cardemil, C. V., Parashar, U. D., & Hall, A. J. (2017). Norovirus Infection in Older Adults: Epidemiology, Risk Factors, and Opportunities for Prevention and Control. Infectious disease clinics of North America, 31(4), 839–870. https://doi.org/10.1016/j.idc.2017.07.012
- Green K. Y. (2014). Norovirus infection in immunocompromised hosts. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, 20(8), 717–723. https://doi.org/10.1111/1469-0691.12761
- Kawagishi, T., Sánchez-Tacuba, L., Feng, N., Costantini, V. P., Tan, M., Jiang, X., Green, K. Y., Vinjé, J., Ding, S., & Greenberg, H. B. (2023). Mucosal and systemic neutralizing antibodies to norovirus induced in infant mice orally inoculated with recombinant rotaviruses. Proceedings of the National Academy of Sciences of the United States of America, 120(9), e2214421120. https://doi.org/10.1073/pnas.2214421120
Sara Christenson
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