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Norovirus Vaccine Pill Shows Promise Against 'winter Vomiting' Bug

An artist's impression of the norovirus

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An early trial of a norovirus vaccine pill has shown promise at protecting against the notorious "winter vomiting" bug, with researchers saying it could potentially be available for use in a few years.

The virus is highly contagious, infecting the stomach and intestines and causing vomiting and diarrhoea. Most people recover within a few days, but very young and older people are especially at risk of ending up in hospital, with significant healthcare costs. "Just in the US alone, it's a 10 billion-[dollar]-a-year problem," says Sean Tucker at biotech company Vaxart in San Francisco, California.

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This has spurred scientists to develop a vaccine, but so far, efforts have failed. That is partly because prior attempts have focused on developing injectable vaccines, which are less good at generating protective antibodies in the intestine, where the virus replicates, says Tucker.

To address this, Tucker and his colleagues previously developed an oral norovirus vaccine that delivers a protein from the GI.1 norovirus variant into the intestine. An initial trial in adults under 50 found that the pill could generate norovirus-specific antibodies in their guts, but people in this age group probably wouldn't be a priority for a vaccine given that they generally recover from the virus easily.

Now, the researchers have tested the vaccine in people in the US aged between 55 and 80. The team gave 11 of them the pill while 22 others took a placebo. About a month later, the researchers collected blood and saliva samples from the participants.

They found the people who took the vaccine had higher levels of IgA antibodies, which can block norovirus from entering cells. These antibodies had increased by more than 10 times in their blood and around seven times in their saliva, compared with samples taken just before vaccination. In contrast, the placebo group saw little change in antibody levels.

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Importantly, the antibodies were still present six months later in the people who took the pill, albeit at lower levels, suggesting it could offer lasting immunity. "The fact that they've got this robust antibody response makes me hopeful that it could provide protection [against infection]," says Sarah Caddy at Cornell University in New York. "In particular, the saliva antibody response is a way we can get a snapshot of what's happening in the intestine – because the immune responses there are similar," she says.

But further work should explore whether the vaccine actually prevents infection or reduces the spread of norovirus, she says. The team hopes to explore this.

What's more, the study focused on just one norovirus variant. "In the real world, there are dozens of different strains you might encounter – the vaccine may not protect against them all," says Caddy. In unpublished work, the researchers found that a version of the vaccine containing both GI.1 and GII.4 norovirus variants – the latter of which is currently surging in the UK – generated antibodies against multiple variants, says Tucker.

This suggests we might soon have a norovirus vaccine, says Tucker. "If everything went smoothly, with no funding hiccups, a vaccine might be available in a couple of years," he says.

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Norovirus Vaccine Hints At Defusing Explosive Stomach Bug In Early Trial

Further, detailed examination of the participants' immune responses showed not only systemic response, but responses in distant mucus membranes. In the blood, two types of antibodies (IgA and IgG) increased by several fold after vaccination compared with the placebo group. The group with the largest responses was the one that received the high dose.

A test that acts as a surrogate for neutralizing antibody responses to norovirus indicated that the antibodies spurred by the vaccine could block the virus. Additional tests found that cellular immune responses were also activated and that the systemic responses result in protection in places far from the intestines—namely the mouth and nose. Saliva tests and nasal swabs found significant jumps in secreted IgA against norovirus.

Immune responses were strongest in the first two months after vaccination and diminished over time, but some persisted for nearly seven months. When the scientists looked at differences between the two age groups (55–65 and 65–80), they didn't see significant differences, suggesting the vaccine was equally effective in the older group.

Overall, the scientists at Vaxart concluded that the vaccine "has the potential to inhibit infection, viral shedding, and transmission."

"Overall, VXA-G1.1-NN administration in older adults led to robust and durable immunogenicity detected both in circulation and multiple mucosal sites, an exciting outcome considering that diminished cellular and mucosal immunity are typical in older populations," they wrote.

The outlook isn't entirely rosy, though—there is some bad news. While immune responses rose in statistically significant measures during this small early-stage trial, it's unclear if that equates to real-life protection. And there's some good reason to be wary. In 2023, Vaxart released results of a challenge study, in which 141 brave souls (76 vaccinated and 65 given a placebo) were deliberately exposed to norovirus to see if the vaccine was protective. The results were weak: 53 placebo-group members (81.5 percent) became infected with norovirus, as determined by a PCR test looking for genetic evidence of the virus in their stool—and so did 76 vaccinated people (60 percent). That worked out to the vaccine offering only a 29 percent lower relative risk of getting infected. Looking at whether infected people developed symptoms of acute gastroenteritis, the vaccine had a protective efficacy of about 21 percent: 34 vaccinated people (48 percent) versus 37 placebo-group members (57 percent) developed symptoms.

Novel Oral Norovirus Vaccine Shows Strong Immune Response

A NEW orally administered norovirus vaccine tablet has demonstrated promising safety and immunogenicity in a clinical trial involving older adults, a group particularly vulnerable to severe outcomes from norovirus infection. The trial assessed the novel vaccine candidate VXA-G1.1-NN, which utilises a nonreplicating adenoviral vector to stimulate immune responses in the small intestine.

The randomised, double-blind, placebo-controlled study enrolled healthy participants aged 55–80 years, divided into two age groups. The vaccine was administered in three different dose levels via a prime and boost schedule, with doses given 28 days apart. The trial aimed to evaluate safety and immunogenicity by measuring antibody responses and mucosal immune markers over a 210-day period. Participants were monitored for adverse events, including local and systemic reactions, to determine tolerability.

VXA-G1.1-NN was well tolerated at all dose levels, with only mild-to-moderate solicited symptoms reported and no serious vaccine-related adverse events. The vaccine induced VP1-specific serum IgG and IgA antibodies in a dose-dependent manner, with levels significantly elevated at 28 days postvaccination and sustained for 210 days.

Functional antibodies were also detected, alongside a robust presence of circulating VP1-specific IgA antibody-secreting cells just one week postvaccination. Additionally, mucosal responses were observed, with VP1-specific IgA increasing in saliva and nasal lining fluid by Day 28 and persisting above baseline through Day 210. The presence of IgA+ plasmablasts expressing the mucosal-homing marker α4β7 further highlighted the vaccine's ability to generate durable immune responses at mucosal sites.

These findings establish that oral administration of VXA-G1.1-NN is both safe and immunogenic in older adults up to 80 years of age. The durable systemic and mucosal responses observed suggest that this vaccine could offer a promising strategy for norovirus prevention in vulnerable populations.

Reference

Flitter BA et al. An oral norovirus vaccine tablet was safe and elicited mucosal immunity in older adults in a phase 1b clinical trial. Sci Transl Med. 2025;17(788):eads0556.

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