There appears to be some good news that vaccines, which may be effective in preventing debilitating norovirus infections, are showing promise in early clinical trials. Despite some early setbacks to one of the vaccines, research continued with other versions of the norovirus vaccine.

I would bet that a new norovirus vaccine would be at or near the top of the wish list for new vaccines.

This post will review the two new norovirus vaccines in clinical trials and give some information on how things are going and when they may become available.

What is norovirus?

According to the CDC, norovirus is a leading cause of acute gastroenteritis, an inflammation of the lining of the stomach and intestines. This can result in intense bouts of vomiting, diarrhea, nausea, and stomach cramps.

Symptoms of norovirus infection usually begin 12 to 48 hours after exposure — the symptoms are often sudden and very unpleasant, but most people will recover without further medical issues. Norovirus is extremely contagious, and anyone can become infected.

Although the virus spreads year-round, infections are most common during the winter months when people tend to spend more time gathered indoors, which makes it easier for infectious diseases like norovirus to spread quickly between individuals.

Infected individuals can shed billions of norovirus particles in their stool and vomit, and it only requires a few virus particles to infect another individual. People usually contract norovirus when the particles end up in their mouths. This can occur through person-to-person contact, consuming contaminated foods or liquids, or touching contaminated surfaces then touching something that goes into your mouth like food. Moreover, norovirus may be transmitted by particles in the air such as in public restrooms.

According to the CDC, norovirus causes about 20 million cases of vomiting and diarrhea, 465,000 emergency room visits, 109,000 hospitalizations, and 900 deaths in the USA. Even though most people recover rather quickly from the infection, a large percentage of those who contract the disease will be hospitalized and about 1% of the hospitalized group will die.

Outbreaks of norovirus have been rising during the past few months. From August 1–October 9, 2024, there were 98 norovirus outbreaks reported by NoroSTAT-participating states in the CDC’s NoroSTAT surveillance program.

Norovirus vaccines in clinical trials

The first of the vaccines is an investigational norovirus mRNA vaccine, trivalent mRNA-1403, from Moderna. According to interim results presented at the IDWeek meeting in October 2024, mRNA-1403 safely elicited strong antibody responses in adults against circulating norovirus genotypes in a phase I/II clinical trial. The phase I portion included 335 healthy younger (up to 49 years) and older (ages 60-80) adults. The phase 2 portion included 616 participants and examined three different single-dose levels in younger (up to 59 years) and older (ages 60-80) adults.

Yes, the vaccine uses the same mRNA technology as Moderna’s COVID and RSV vaccines.

The Moderna vaccine contains three mRNAs that encode for the major capsid protein 1 (VP1) of three globally prevalent norovirus genotypes — GII.4, GI.3, and GII.3. The reason this is done is because there are over 48 different genotypes of norovirus, but this trivalent vaccine covers the most prevalent.

The key results that were presented at IDWeek were:

• A single injection of mRNA-1403 stimulated robust antigen-blocking antibodies and serum virus-like particle antibodies by day 29 against three virus genotypes in younger and older adults across all dose levels, when compared with placebo.
• As for safety signals, the vaccine was well tolerated across dose levels tested in both younger adults (up to age 59) and older adults (ages 60-80) and throughout phase I and phase II follow-up periods. Systemic reactions that occurred more frequently in the vaccine group when compared with the placebo group included headache, fatigue, and nausea. There were no serious adverse events or adverse events that led to study withdrawal throughout 8 months of follow-up during the phase I portion of the study and through 1 month of follow-up in phase II.

Based on the phase I/II clinical trial results, Moderna has initiated a phase III trial to evaluate the effectiveness of a single dose of the mRNA-1403 vaccine to prevent moderate to severe norovirus acute gastroenteritis. The study intends to enroll over 20,000 adults in the US, Japan, Canada, Puerto Rico, and the UK. Of course, if you want to participate in this clinical trial,

The second one, an oral vaccine, VXA-G1.1-NN from Vaxart, is a stable, oral, enteric-coated tablet that dissolves in the small intestine. The Vaxart vaccine uses an adenovirus vector, which “carries” the genes for the norovirus antigens to the cell which will reproduce the protein, and then induce the immune response. The adenovirus then injects its DNA into the nucleus. The adenovirus is engineered so it can’t make copies of itself, but the gene for norovirus antigens can be read by the cell and copied into a molecule called messenger RNA, or mRNA. At this point, these vaccines work like the mRNA vaccine technology.

Vaxart just completed its phase I clinical trial with some mixed results. The study included 141 healthy adults ages 18 to 49. Participants were randomized to receive the vaccine (n=76) or placebo (n=65). All participants were then given a large challenge dose of norovirus on day 29 after vaccination. Investigators measured norovirus infection and illness rates in the two groups between days 33 and 36.

The key results were:

• The vaccine was associated with a 29% relative reduction in norovirus infection compared with placebo.
• Unfortunately, it did not meet its primary endpoint for preventing illness, showing a statistically non-significant 21% relative reduction.
• Post-challenge, vaccination resulted in a 35% relative reduction in the incidence of emesis as well as large reductions in viral shedding in vomitus and stool.

Summary

The results from these early clinical trials show that we might have two different vaccines for the prevention of norovirus vaccines. However, these results are from phase I/II trials for the Moderna vaccine and phase I for the Vaxart vaccine. At best, we are probably at least two years away from FDA-approved versions, but I tend to make conservative estimates of the approval timing for vaccines.

Norovirus is a dangerous disease, causing numerous hospitalizations and deaths in the USA alone. Preventing it would be a major public health success.

Citations

• Cannon JL, Bonifacio J, Bucardo F, Buesa J, Bruggink L, Chan MC, Fumian TM, Giri S, Gonzalez MD, Hewitt J, Lin JH, Mans J, Muñoz C, Pan CY, Pang XL, Pietsch C, Rahman M, Sakon N, Selvarangan R, Browne H, Barclay L, Vinjé J. Global Trends in Norovirus Genotype Distribution among Children with Acute Gastroenteritis. Emerg Infect Dis. 2021 May;27(5):1438-1445. doi: 10.3201/eid2705.204756. PMID: 33900173; PMCID: PMC8084493.