Norovirus is a highly contagious virus that infects mucosal tissues in the gut and causes approximately 20 million cases of acute gastroenteritis annually in the United States (1). It leads to 70,000 hospitalizations, up to 800 deaths, and an estimated $10.6 billion in healthcare costs (2). While most people generally recover after an uncomfortable few days, norovirus poses a significant threat to older adults, particularly those with weakened immune systems or underlying conditions. Yet no vaccine is currently available to mitigate its effects. Now, a Phase 1b trial of VXA-G1.1-NN, an oral norovirus vaccine candidate developed by Vaxart, offers new hope (3).
“Norovirus is quite a challenge for us to deal with because it can survive on environmental surfaces for up to a month,” said Brian Labus, an epidemiologist and biostatistician at the University of Nevada, Las Vegas who did not participate in this work. It only takes around 10 viral particles for someone to get infected with norovirus, and a sick person produces billions of viral particles. “Every person that gets norovirus basically produces enough to infect everybody on the planet,” he added.
Every person that gets norovirus basically produces enough to infect everybody on the planet.
- Brian Labus, University of Nevada, Las Vegas
The VXA-G1.1-NN vaccine is a non-replicating adenovirus that expresses a norovirus capsid protein. It is delivered as a small tablet designed to bypass the stomach and release its contents in the last part of the small intestine. Once there, the vector enters epithelial cells, triggering immune responses in the blood, nose, mouth, and intestine, as shown in a previous Phase 1 study in healthy adults 18 to 49 years of age (4).
To gauge the vaccine’s safety and efficacy in older adults, the researchers enrolled 65 participants aged 55 to 80 who received two doses of either the oral VXA-G1.1-NN vaccine tablets — at a low, medium or high dose — or matching placebo tablets.
The oral vaccine did not cause any serious or grade 3 adverse events (AEs) and was well tolerated regardless of the dose, with only mild to moderate related AEs reported. The most commonly reported AEs were headache and malaise/fatigue, which occurred at similar rates in both the vaccine and the placebo groups. Fewer AEs were reported after the second dose.
The vaccine led to dose-dependent systemic and mucosal immune responses, including viral protein 1 (VP1)-specific immunoglobulin G (IgG), immunoglobulin A (IgA), and functional antibodies, which persisted above baseline for up to 210 days.
Vaxart’s novel oral pill vaccine approach triggers a first line of defense against viral pathogens.
Credit: Vaxart
Prior to this trial, the team at Vaxart wasn’t sure what to expect, as it’s well known that vaccines in individuals over 65 often require either a higher dose or a different formulation to elicit a strong immune response. “We were thrilled to see that our vaccine did just as well in the older population, up to 80 years old, compared to individuals who were up to 49 years old,” said study first author Becca Flitter, the Director of Immunology at Vaxart.
This vaccine’s ability to generate immunity at the mucosa — the entry point of the norovirus — is particularly significant. “It’s really tricky to get that kind of response from an injected vaccine,” Flitter said.
Labus said, “This is an interesting approach to trying to prevent norovirus — it's something that has the potential to be a game changer if we can have a vaccine that can affect multiple strains.” But, he added, “There are a lot of challenges in going from this early Phase 1 work until bringing it to market.”
If everything goes well, Flitter hopes the vaccine will be publicly available in two to three years.
References
- Hall, A.J. et al. New insights into the global burden of noroviruses and opportunities for prevention. Expert Rev Vaccines 15, 949–951 (2016).
- Bartsch, S.M. et al. The Clinical and Economic Burden of Norovirus Gastroenteritis in the United States. J Infect Dis 222, 1910–1919 (2020).
- Flitter, B.A. 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 17, eads0556 (2025).
- Kim, L. et al. Safety and immunogenicity of an oral tablet norovirus vaccine, a phase I randomized, placebo-controlled trial. JCI Insight 3, e121077 (2018).
