Norovirus conjures a nightmarish series of gastrointestinal symptoms, and the hated infection has been rampant this winter. The so-called stomach flu—although it’s unrelated to influenza—strikes suddenly and curses its victims with one to three days of diarrhea and vomiting.
Yet unlike other commonplace infections such as seasonal flu and COVID, no vaccine exists to help people avoid being sidelined by norovirus, a notoriously transmissible and resilient virus that is difficult to kill with common alcohol-based disinfectants. Vaccine developers have long worked to create a vaccine—some seven different candidates are currently in various stages of clinical trials. But none has proved effective enough to earn approval in the U.S. There are several scientific barriers, but researchers hope that soon one approach will meet the challenge and provide an effective tool to those who want to boost their immune system against the nasty infection.
What Is Norovirus?
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Norovirus is responsible for more than half of foodborne illness cases in the U.S. The virus can survive for up to two weeks on surfaces, flourishes in the face of common hand sanitizers and rips through settings such as cruise ships and cafeterias. Typical symptoms of infection include diarrhea, vomiting, nausea and stomach pain; people can also experience fever, headache and body aches. Cases with severe vomiting and diarrhea increase the risk of serious dehydration.
The Centers for Disease Control and Prevention’s data regarding norovirus outbreaks are quite limited: the agency’s surveillance network for the infection includes only 14 states. Still, the picture these statistics paint is grim. The reporting states have seen 1,078 suspected or confirmed norovirus outbreaks from August 1, 2024, through January 15, 2025, which is nearly twice as many as the same period during the 2023–2024 season and higher than in all years since at least 2012, when the reporting network was established.
Young children and people aged 65 and older are particularly vulnerable to severe illness. Each year the virus causes more than two million outpatient clinic visits, predominantly in young children, and kills about 900 people a year, mostly those aged 65 and older. The infection is highly contagious, causes large outbreaks often and hits these vulnerable groups hard—but for most people, symptoms only last a few days. That variability in disease severity presents a tricky situation for would-be vaccine manufacturers, says Ming Tan, a scientific researcher at the Cincinnati Children’s Hospital Medical Center.
“Some people do not view it as a very important disease, and other people say that it’s terrible because it can make a lot of people sick in certain close settings,” Tan says.
Challenges for Vaccine Makers
The virus boasts several characteristics that make it a challenging target for vaccine developers. First, as with influenza, “norovirus” is actually a group of viruses that consists of some 48 so-called genotypes divided into 10 larger classes. As with the flu, an immune system trained to recognize one variety of norovirus can’t necessarily protect against the others. And dominant strains come and go as frequently as every two to four years, making it difficult for the immune system to keep up. (Cases this year and last year have been caused predominantly by a strain called GII.17, whereas previous seasons had been led by a strain nicknamed Sydney.)
“There are dozens of genotypes of norovirus that can cause disease in humans, and each one of those genotypes has a slightly different-looking protein shell that we think requires a slightly different immune response,” says Doran Fink, a physician and vaccine scientist at the biotech company Moderna, who leads its norovirus vaccine development.
Another challenge is that norovirus causes what scientists call a mucous membrane, or mucosal, infection—in this case, a local infection in the intestinal surface tissue. (Flu is a localized mucosal infection in respiratory tissue.)
These local viruses are trickier for the body to remember and fight off compared with systemic infections, such as measles and chickenpox, that affect the whole body and usually cause robust, long-lasting immune responses. “Mucosal immunity is short-lived, not like systemic immunity,” says Lijuan Yuan, a viral immunologist at Virginia Tech. An injected vaccine triggers a systemic immune response, she notes, not a mucosal one, so it is less able to access the virus. This disconnect makes it more likely that injected vaccines for mucosal infections will only protect against severe disease, not prevent sickness entirely.
Norovirus is also tricky to work with in the lab. Preliminary vaccine experiments typically require animal models, but researchers don’t have a good such model for norovirus. That’s because human noroviruses don’t easily infect animals, and animal-specific noroviruses cause very different symptoms. Norovirus can’t be grown well in cells either, Yuan notes.
In the Pipeline
Despite the host of obstacles, scientists are working on clinical trials testing half a dozen different vaccine candidates. All target the primary surface protein—or capsid protein—that encases a norovirus molecule, but they use several different approaches, each with its own strengths and weaknesses.
In one approach, scientists produce many of these so-called capsid proteins. The proteins then spontaneously form empty structures in the same shape as the virus. When these empty shells, called viruslike particles, are injected into a person, the body reacts as it would to the real thing, training the immune system. But making the viruslike particles is time-consuming, Tan says. And although the vaccine produced decent results in trials in adults, it did little to protect children, suggesting that this vulnerable population may require a different vaccine.
A second approach recruits a common, typically mild respiratory virus called an adenovirus, makes it unable to replicate and gives it the ability to produce the target norovirus protein. The adenovirus is packaged into an oral vaccine, which is much easier to administer than an injection, and it can train the mucosal immune system directly. The protection rate is still rather low, however, Tan says.
The third approach uses the same mRNA technology that was used to create some of the COVID vaccines. Genetic information for the norovirus protein is injected into the vaccine recipient to trigger the immune response. This method is simpler to execute and can be more easily updated as different strains of norovirus become dominant, Fink says. His team at Moderna designed an mRNA norovirus vaccine, and the company is now recruiting people to test how protective it is. That will enable scientists to compare the mRNA technique with the viruslike particle and adenovirus approaches that have disappointed researchers to date. “Whether or not it will have a better efficacy, we still need to wait [and see],” says Tan, who is not involved with any of these candidates.
Whichever vaccine makes it through trials first may not earn the annual ritual status of the flu shot. A norovirus vaccine would likely be offered first to people aged 65 years and older as well as immunocompromised people, given that norovirus infections tend to be much worse for these groups, Fink says. It would probably be offered as a yearly dose timed with the peak period for norovirus, which is between November and April in the Northern Hemisphere. Perhaps people planning to embark on a cruise or those who otherwise expect to be exposed to the virus could opt for a dose as well, he notes. But Tan isn’t convinced that healthy adults would be very interested in a norovirus vaccine.
Fink says that there’s still value in having a vaccine as a prevention option, even if it won’t be fully protective. “If we can shift the burden of disease such that even if you do get norovirus, it’s very mild, I think that would be a big success,” he says.