Vaxart's Oral Norovirus Vaccine: Key Study Findings and Future Plans

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Sean Tucker, PhD, highlights effective immune response and mucosal immunity, paving the way for broader applications in viral disease prevention.

Vaxart, Inc recently published complete data from its phase 1b trial of its first-generation oral norovirus vaccine, demonstrating encouraging results in elderly adults. The study showed that the vaccine was capable of inducing strong antibody and T-cell responses in adults aged 55-80 years, a group known to experience weakened immune responses to traditional injectable vaccines. The vaccine triggered significant increases in serum anti-VP1 IgA and IgG antibodies and mucosal T-cell responses, with no significant differences observed between the older adults and younger populations previously studied.

In our interview with Sean Tucker, PhD, chief scientific officer at Vaxart, he spoke about the study and its implications, explaining that, "From the standpoint of a reference point, many injectable vaccines are known to work less efficiently in older adults, and the way that these have been souped up to make them work better is to add more antigen or an adjuvant. And what we wanted to know in this study [was], can we see whether our vaccine works well in the older population? And the good news, from our standpoint, is that there didn't seem to be any differences in the immune responses we got compared to what we'd seen in prior studies in younger adults." This finding suggests that the oral vaccine may not require significant adjustments to be effective in elderly adults.

The study also revealed that although the vaccine is designed to target the intestine, it was effective in generating antibody responses not only in the intestinal tract but also in the nose and mouth—areas potentially crucial for protecting against respiratory infections. "While this vaccine is designed to go into the intestine, we also saw some really great increases in antibody responses in the nose and the mouth, which could be even more important for things like COVID or flu, where pathogens usually invade through the nose," Tucker said. This mucosal immunity could have broader applications, particularly in preventing the transmission of respiratory viruses.

Looking ahead, Vaxart is progressing to second-generation norovirus vaccine candidates. Tucker revealed that the company is already working on these candidates, which have shown improved immunogenicity in animal models. The company plans to move these forward into clinical trials, with data expected by mid-2025. "Our expectation, of course, is that these new candidates will do much better, and our plan is to push it forward into late-stage trials after that," Tucker added.

Vaxart's oral vaccine platform is designed to overcome challenges associated with traditional vaccines, including cold storage and needle-stick injuries. With recent outbreaks of norovirus across the country, Tucker addressed the potential for the vaccine to reduce transmission. He explained, "One of the big advantages of our vaccine candidate is that it should do a better job of protecting against getting the virus. We've shown in a norovirus challenge study that our vaccine was able to suppress the amount of virus that was actually being secreted. This could be really important for blocking or inhibiting transmission, even in cases of breakthrough infections."

As the company moves forward with its second-generation vaccines, Vaxart's innovative oral platform could play a key role in not only preventing norovirus infections but also potentially offering protection against other viral diseases through mucosal immunity.

Reference
Flitter BA, Greco SN, Lester CA, 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):eabc1234. doi:10.1126/scitranslmed.abc1234
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