Why is there no norovirus vaccine for stomach flu?

Every yearBetween 19 and 21 million Americans suffer from gastroenteritis (aka “stomach flu”), most commonly caused by a group of pathogens called norovirus. These infections lead to hundreds of thousands of emergency room visits and hospitalizations, as well as approximately 900 deaths, each year. This winter, norovirus infections are particularly bad in the United States, according to the CDC, which is recording the highest number of outbreaks in the last decade.

There are two possible reasons for the current increase, said Daniel Kuritzkes, chief of infectious diseases at Harvard Medical School. Forbes. The first is that the strains of viruses in circulation change each year, which reduces immune protection in the same way as the flu and Covid. Additionally, people’s immunity to particular strains of norovirus wanes over time, making reinfections possible.

Much to the dismay of parents, teachers and cruise enthusiasts, there is no approved treatment for norovirus infections, nor any vaccine against them. A treatment for norovirus is unlikely to be developed, Kuritzkes notes, because the viral infection typically lasts about a day or two, making it difficult for regulators to demonstrate a benefit. Additionally, the main complication leading to hospitalizations is dehydration, which is easily treated with IV fluids.

This makes the vaccine the most promising route to currently combating noroviruses. There are currently three vaccine candidates in human clinical trials, and the most advanced is Moderna, which has developed a norovirus vaccine with the same mRNA technology as the Covid-19 vaccine. Being first to market offers great opportunity, given that annual virus infections cost the global economy an estimated $60 billion, including direct healthcare costs as well as indirect costs such as losses productivity. Moderna estimates that a norovirus vaccine represents a total addressable market of approximately $3 billion to $5 billion.

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One of the main challenges of developing a norovirus vaccine, said Doran Fink, who leads Moderna’s development efforts, is that, as with the flu, dozens of strains can be circulating at the same time, and these Strains often do not have common characteristics. characteristics recognized by the immune system. Immunity to one strain will not necessarily protect you against another. That’s why Moderna’s vaccine currently targets three viruses at once, and there is another vaccine in early stages of development that can target five. This is similar to seasonal flu vaccines, which are newly generated each year to target multiple strains based on what they are predicted to be circulating.

What makes things easier, Fink said, is that one particular strain, called GII.4, has been responsible for the majority of outbreaks over the past decade. By targeting GII.4 and two other circulating strains, he said, Moderna’s vaccine “might be able to cover upwards of 70 or 80 percent of the norovirus outbreaks that might occur in a given year.” And with our mRNA technology, we would be able to update the composition of the vaccine to respond to changes in which genotypes might circulate over time.

Another challenge for norovirus vaccines, Kuritzkes said, is that they attack the body in the gastrointestinal tract, meaning a vaccine must promote enough neutralizing antibodies there to prevent infection. . “Developing this type of vaccine has been a scientific challenge,” he said. It is not impossible, however, as the approved vaccines against rotavirus and cholera attest.

Last summer, HilleVax, a company launched by Takeda Pharmaceuticals and Frazier Healthcare Partners to develop a norovirus vaccine, saw its stock price fall last July when it announced that its vaccine candidate had proven ineffective to prevent infections in infants. The company said it was pausing development of the vaccine for infants, although it was continuing it for adults.

Targeting the gastrointestinal tract is one of the goals of another company, Vaxart, which is developing a norovirus vaccine that is taken as a pill rather than an injection. Its vaccine is currently in the early stages of human testing, but Kuritzkes sees the approach as promising. “As with typhoid and cholera, an oral vaccine makes a lot of sense because it’s about stimulating the immune response at the site,” he said.

Fink acknowledged the challenges of getting antibodies into the gastrointestinal tract and said the company was actively monitoring this as part of its development process. However, he noted that antibodies migrate to the gastrointestinal tract in other experimental norovirus vaccines. Additionally, vaccines with similar technology show that antibodies can migrate: for example, with Moderna’s Covid-19 vaccine, antibodies travel to sites of infection in the nose.

Moderna administered its first patient in a global Phase 3 clinical trial (usually the last test before seeking regulatory approval) in September last year. Fink said testing is expected to include about 25,000 patients and will last about two years. Which means that even if a trial were successful, it probably wouldn’t be until 2027 or later that its vaccine would hit the market.

Until then, Kuritzkes said it’s important to remember that unlike respiratory viruses, noroviruses are “incredibly resilient” and can survive on surfaces and even resist hand sanitizer. The best defense against this, he added, is to “wash your hands with soap and water,” he added. “Personal hygiene is the most important thing to protect yourself.”

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