Guillain-Barré Syndrome Risk Identified in Norovirus Vaccine Candidate

With cruise ship voyages reporting additional norovirus outbreaks in 2025, vaccines that protect people against human norovirus disease are in demand.

Historically, developing a broadly effective norovirus vaccine has been challenging owing to the genetic and antigenic diversity of noroviruses.

Another concern has arisen due to Moderna Inc.'s recent announcement.

On February 14, 2025, Moderna stated the two-season Phase 3 clinical study evaluating the efficacy, safety, and immunogenicity of the Company's trivalent vaccine against norovirus (mRNA-1403) has been placed on U.S. FDA clinical hold following a single adverse event report of a case of Guillain-Barré syndrome (GBS). This case is currently under investigation.

Moderna's press release says the Company does not expect an impact on the mRNA-1403 study's efficacy readout timeline, as enrollment in the Northern Hemisphere has already been completed. The timing of the Phase 3 readout will depend on case accruals.

According to a report by Fierce Biotech, Moderna's president, Stephen Hoge, M.D., expanded on this announcement, pointing out that "GBS does happen."

Each year in the United States, 3,000 to 6,000 people develop GBS, some related to vaccination.

For example, since January 7, 2025, the U.S. FDA has required a GBS warning in the Prescribing Information for certain approved RSV vaccines during the 42 days following vaccination.

According to the U.S. CDC, GBS is a rare disorder where the body's immune system damages nerves. To study whether a new vaccine might cause GBS, the CDC compares the usual GBS rate to the observed GBS rate in vaccinated people.

While its cause is not fully understood, the syndrome often follows infection with a virus or bacteria. Most people fully recover from GBS, but some have permanent nerve damage, adds the CDC.

Other norovirus vaccine development efforts include HillVax. In November 2024, HillVax announced it was exploring the potential for continuing to develop its investigational virus-like particle-based bivalent norovirus vaccine candidate.

Separately, Vaxart Inc.'s orally administered bivalent GI.1/GII.4 norovirus oral vaccine candidate is differentiated from others because it generates systemic and mucosal immunity delivered through the mouth and is stable at room temperature. On January 14, 2025, Vaxart stated it would proceed with a Phase 1, open-label, dose-ranging clinical trial, expected to initiate in the first half of 2025.

With about 20 million norovirus illnesses yearly in the United States, vaccine development activities targeting this disease will continue to be watched closely in 2025.