Norovirus is a highly contagious virus and a primary cause of acute gastroenteritis, often called the “stomach flu.” It spreads easily through contaminated food, water, and surfaces, as well as direct contact with an infected person. This ease of transmission causes millions of cases annually across the globe, leading to widespread outbreaks in community settings like schools, hospitals, and cruise ships.
Current Availability of a Norovirus Vaccine
There is currently no licensed vaccine available to the public for preventing norovirus. As of mid-2025, regulatory bodies like the U.S. Food and Drug Administration (FDA) have not approved any norovirus vaccine for commercial use. Therefore, prevention relies on methods like frequent hand washing, careful food handling, and disinfecting contaminated surfaces to reduce the risk of infection. The absence of a vaccine leaves populations vulnerable to the illness.
Obstacles to Vaccine Development
Developing a norovirus vaccine presents scientific challenges rooted in the virus’s biology. A primary hurdle is the immense genetic diversity of norovirus. The virus is classified into numerous genogroups and genotypes, with strains from genogroups I (GI) and II (GII) causing the vast majority of human infections. A broadly effective vaccine must be polyvalent, meaning it needs to protect against multiple, co-circulating genotypes.
Another challenge is the virus’s rapid evolution. Norovirus mutates frequently through a process known as antigenic drift, which is pronounced in the dominant GII.4 genotype. This evolution allows the virus to create new variants that can evade the immune system’s memory from previous infections. This constant shifting is similar to the influenza virus, suggesting a norovirus vaccine might need regular updates to match newly emerging strains.
A third obstacle is the nature of human immunity to norovirus. Natural infection does not confer long-lasting protection, as studies show immunity may last only from a few months to a couple of years before a person can be reinfected. This transient immunity is a problem for developers, who aim to create a vaccine that induces a more durable response than natural exposure. The duration of vaccine-induced immunity is a question that ongoing clinical trials seek to answer.
Norovirus Vaccines in Clinical Trials
Several vaccine candidates are progressing through clinical development using different technological platforms. These candidates are evaluated in a series of human studies, from Phase 1 safety trials to Phase 2 efficacy studies, and finally to large-scale Phase 3 trials to confirm effectiveness before seeking approval.
One approach involves Virus-Like Particles (VLPs), which are engineered proteins that mimic the norovirus’s outer shell but contain no genetic material, making them non-infectious. Takeda’s VLP-based vaccine candidate, TAK-214, was designed to protect against the GI.1 and GII.4 genotypes. Though it showed promise, the candidate, later licensed to HilleVax as HIL-214, did not meet its primary endpoint in a trial focused on infants.
Another strategy is messenger RNA (mRNA) technology. Moderna is developing an mRNA-based vaccine, mRNA-1403, to provide protection against multiple norovirus strains. This vaccine entered a large Phase 3 trial in 2024, but the FDA placed it on a clinical hold in early 2025 following a reported adverse event.
Vaxart is developing an oral tablet vaccine that uses a modified adenovirus as a vector to deliver genetic instructions for a norovirus protein to intestinal cells. The goal is to stimulate a mucosal immune response directly at the site of infection. An early trial of this oral vaccine showed it could trigger protective antibodies and may reduce the amount of virus shed by infected individuals, which could help limit transmission.
Potential Impact and Target Populations
A norovirus vaccine would have a substantial impact on public health by reducing the millions of annual infections that lead to healthcare costs and productivity losses. A vaccine would also decrease hospitalizations, particularly those resulting from severe dehydration, a common complication of norovirus gastroenteritis.
Vaccination efforts would prioritize populations at the highest risk for infection and severe outcomes. These groups include:
- The elderly, especially those in long-term care facilities where outbreaks are frequent.
- Young children under five, who are highly susceptible to severe disease.
- Military personnel living in close quarters.
- Travelers on cruise ships, where enclosed environments facilitate rapid transmission.