Vaxart is developing an oral vaccine for norovirus, aiming to provide a simple and accessible solution for a virus that currently lacks any approved vaccines or targeted treatments. Norovirus is known for causing repeated infections and remains the leading cause of vomiting and diarrhea from acute gastroenteritis in the United States. The global economic impact of norovirus amounts to about $60 billion each year in healthcare expenses and lost productivity, according to the CDC.
Sean Tucker, founder and chief scientific officer at Vaxart, explained the company's approach: “Even if it’s the same strain,” he said, referring to how people can be infected multiple times by norovirus. He added, “Vaxart wanted to ‘build something that’s simple, cheap and easy to use, and give that as a vaccine. Because it’s hard to develop long-term immunity, just handing out tablets every year would be very simple.’”
Tucker believes that oral administration offers advantages over traditional injections: “It’s not an injection; it’s a pill.” To create their candidate vaccine VXA-G1.1-NN, Vaxart used a viral vector system similar to those used in some gene therapies. The method involves packaging a norovirus antigen inside a non-replicating adenovirus along with double-stranded RNA as an adjuvant designed to trigger immune responses specifically in the gut.
One technical challenge was ensuring the viral vector could survive passage through the digestive system. “We had to learn how to tablet it without crushing the biological entity,” Tucker noted.
Results from clinical trials have shown promise for Vaxart's approach. In its Phase 2b trial announced in May 2025, volunteers who received VXA-G1.1-NN experienced 30% fewer infections after exposure compared with those given placebo. Earlier studies also indicated strong immune responses at mucosal surfaces where norovirus first attacks.
Vaxart plans to start a Phase 3 trial early this year.
Other companies pursuing norovirus vaccines have encountered setbacks. Takeda transferred development of its injectable candidate—based on virus-like particles—to HilleVax in 2021; however, this program failed its Phase 2 trial in 2024. Moderna began testing its mRNA-based vaccine (mRNA-1403) in September 2024 but faced delays due to regulatory holds following safety concerns and difficulties enrolling enough participants after resuming trials later on. Recent uncertainty about Moderna's overall vaccine pipeline has grown after the FDA declined review of its flu vaccine application.
Tucker said lessons from other seasonal viruses could inform future distribution strategies: “[Flu] is a good model,” he said. “We could change the strain every year if we needed to.” He emphasized targeting populations most affected by norovirus outbreaks—such as families with children or cruise ship travelers—especially during peak seasons: “We’re going to provide protection through the worst time, which is winter for norovirus,” Tucker stated. “It’s called winter vomiting disease for a reason.”
