Why a norovirus vaccine isn’t available — yet

Norovirus has been top of mind for many this winter: Everybody seems to know somebody that’s been temporarily felled by the winter vomiting bug.

The anecdotal sense that norovirus is everywhere has been born out in some data so far. From August to mid-January, there were about twice as many outbreaks than there were in the same time period a year ago: 1,078 compared with 557, according to the U.S. Centers for Disease Control and Prevention. Those data come from 14 states that partner with the CDC on norovirus surveillance.

Norovirus symptoms come on strong and make for a few extremely unpleasant days of vomiting, diarrhea and nausea. People tend to be fine once they’re through it. But it can be harder on the youngest, the oldest and those who are immunocompromised, with dehydration a particular problem. There are no vaccines or specific treatments for the virus.

Around 20 million illnesses, on average, are caused by norovirus each year in the United States, as per the CDC. That leads to 465,000 emergency department visits — mostly for young children — and 900 deaths, largely among those 65 and older. Globally, there are 685 million norovirus illnesses each year and 200,000 deaths, with a quarter of those in children, mainly in developing countries.

The burden and cost of norovirus illnesses globally — estimated at $4 billion for healthcare plus a $60 billion cost to society annually — has made a vaccine for this virus a World Health Organization priority. There are several candidates making their way through clinical trials now. But the virus is a tricky one, and there are still some big information gaps to fill. Here’s an introduction to the virus, some of the vaccines in development and how to keep a norovirus infection at bay.

What do researchers know about norovirus and what big questions remain?

There are a lot of noroviruses out there, so researchers keep track of them with a classification system. Based on genetic differences, noroviruses are divided into 10 groups and subdivided into 49 types. Five of the groups are known to infect people. Type 4 in group 2, represented as GII.4, has been responsible for most norovirus illnesses in people for the last two decades or so, but other types have caused outbreaks too. Looking at September through December of 2024, most of the norovirus outbreaks in the United States were due to GII.17, according to the CDC.

Some of the norovirus groups infect other mammals, including cows, sheep, dogs, cats and sea lions. Oysters in coastal areas contaminated with sewage discharge can pick up norovirus, which is why the shellfish are sometimes tied to outbreaks.

One big question about the virus is that researchers aren’t sure how long immunity lasts after a norovirus infection in people, with estimates ranging from several months to nine years, depending on the study. People can become infected by one after another of the different types, but whether that’s due to short-lived immunity, the genetic differences between the types or a combination of those and other factors isn’t known. And GII.4, the type behind most norovirus illnesses in people, is especially prone to genetic changes, such that people can be reinfected by the different versions of this one type.

Another lingering question: In people, norovirus infects the cells that line the inner surface of the intestine, which are called epithelial cells. But researchers haven’t figured out what receptor the virus uses to break in. The virus does bind to certain sugars on the cells, but evidence so far suggests that only helps the virus hang on, says virologist Christiane Wobus of the University of Michigan in Ann Arbor. “We don’t know what molecule helps the virus cross over the membrane to get inside the cell to then start to replicate.”

Noroviruses that infect people have been difficult to study because researchers haven’t been able to get them to grow in laboratory cell cultures. There’s been a breakthrough on that front: the development of mini guts, which are lab-grown cultures of intestinal cells that physiologically function like the lining of the gut. Mary Estes, a molecular virologist at the Baylor College of Medicine in Houston, and her colleagues were the first to show that norovirus will replicate in mini guts. “We’re now just beginning — because now we have the cultivation systems — to look at the biology” of the virus, Estes says.

When researchers figure out the receptor norovirus uses to enter cells, they should be able to incorporate that receptor in basic laboratory cells “that every virologist in the world could work with,” Estes says, making norovirus research much easier.

What’s challenging about developing norovirus vaccines and what progress has been made?

“The biggest problem we have to deal with is the genetic diversity — there’s lots of different flavors” of norovirus, Wobus says. Considering that diversity, researchers aren’t sure how many norovirus types a vaccine needs to include in order to provide enough protection, she says, other than representatives from groups I and II, which are responsible for a lot of infections.

Even with those questions, “it’s definitely good that there are multiple vaccine platforms that are being tested,” Wobus says.

The candidates moving through clinical trials target the protein shell of the virus. Moderna announced last September that it has begun the phase 3 trial of their norovirus vaccine candidate. The trial’s goal is to enroll 25,000 people globally: 20,000 age 60 and older and 5,000 ages 18 to 59. Researchers will evaluate how well the pharmaceutical company’s mRNA vaccine, which includes three norovirus types, protects against moderate to severe cases of illness.

Other candidates that have made it through early-stage clinical trials are based on viruslike particles, which mimic the shape and size of a virus but can’t cause infections because they don’t contain genetic material.

“I think there will be a vaccine,” Estes says. But it’s hard to say when until there are results from phase 3 trials.

How can people try to avoid norovirus infections?

A person experiencing norovirus symptoms is extremely infectious. The virus particles spread via feces and vomit. Some studies have suggested it doesn’t take very many virus particles to infect someone else. If you’re helping clean up after someone who is dealing with symptoms, use gloves and a mask “because particles are in the air,” Wobus says. “It always surprises people how far vomit particles travel.”

The end of symptoms does not mean the end of the infection. People can continue to excrete the virus for weeks. “We certainly can detect it in people’s stool for out to a month,” Estes says.

The virus is also very stable in the environment, meaning it doesn’t degrade quickly. When scientists investigated a 2014 norovirus outbreak at two hotels in Spain, they detected the virus on frequently touched surfaces in the guest rooms sampled as well as on elevator keypads, scientists reported in 2020 in a journal of the Spanish Society of Infectious Diseases and Clinical Microbiology.

“The virus sticks to lots of different surfaces” and remains for a long time, Estes says. “So other people coming along that touch those surfaces can pick it up. And if you put your hands in your mouth or on your face, you can get infected.” And, unfortunately, alcohol-based hand sanitizers do not kill the virus. Washing hands with soap and water is the way to go.