Every year, somewhere between 19 and 21 million Americans come down with gastroenteritis (aka “stomach flu”), most often caused by a group of pathogens called noroviruses. These infections lead to hundreds of thousands of ER visits and hospitalizations, as well as around 900 deaths, every year. This winter, norovirus infections are particularly bad in the U.S., according to the CDC, which is recording the highest outbreak numbers of the last decade.
There are two possible reasons for the current surge, Daniel Kuritzkes, chief of infectious diseases at Harvard Medical School told Forbes. The first is that strains of circulating viruses change each year, which reduces immune protections similarly to influenza and Covid. Additionally, people’s immunity to particular strains of norovirus wane over time, making reinfections possible.
Much to the consternation of parents, teachers and cruise ship enthusiasts, there are no approved treatments for norovirus infections, nor is there any vaccine against it. A treatment for norovirus is unlikely to be developed, notes Kuritzkes, because the viral infection typically lasts just about a day or two, making it hard to demonstrate a benefit to regulators. Additionally, the primary complication that leads to hospitalizations is dehydration, which is easily treated with IV fluids.
This makes a vaccine the most promising avenue for fighting noroviruses right now. There are currently three vaccine candidates moving through the clinical pipeline in human trials right now, and the furthest along is Moderna, which has developed a norovirus vaccine with the same mRNA technology as the one for Covid-19. Being the first to market provides a big opportunity, given that annual infections of the virus cost the global economy around $60 billion, including both direct healthcare costs as well as indirect costs such as productivity losses. Moderna estimates that a norovirus vaccine has a total addressable market of about $3 to $5 billion.
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One of the main challenges of developing a vaccine against norovirus, said Doran Fink, who leads Moderna’s development efforts, is that like the flu, there are dozens of strains that might be circulating at one time, and these strains often don’t have common features that are recognized by the immune system. Immunity to one strain won’t necessarily protect you from another. That’s why Moderna’s vaccine currently targets three viruses at once, and it has another vaccine in earlier 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 forecasts of which are expected to be circulating
Something that makes this easier, said Fink, is that one particular strain, called GII.4, has been responsible for a majority of outbreaks for the past decade. By targeting GII.4 and two other circulating strains, he said, Moderna’s vaccine “could be able to cover upwards of 70 or 80% of the norovirus outbreaks that might occur in a given year. And with our mRNA technology, we would be able to update the vaccine composition in order to respond to changes in which genotypes might circulate over time.”
Another challenge for norovirus vaccines, said Kuritzkes, is that it attacks the body in the gastrointestinal tract, which means a vaccine needs to promote enough neutralizing antibodies at that location to prevent infection. “Developing those kinds of vaccines has been scientifically challenging,” he said. It’s not impossible, though, as approved vaccines for rotavirus and cholera attest.
Last summer, HilleVax, a company launched by Takeda Pharmaceuticals and Frazier Healthcare Partners to develop a norovirus vaccine, saw its share price plummet last July when it reported that its vaccine candidate proved ineffective at preventing infections in infants. The company said it was halting development of the vaccine for infants, though it’s still pursuing it for adults.
Targeting the GI tract is one of the goals of another company, Vaxart, which is developing a norovirus vaccine that’s taken as a pill, rather than an injection. It’s currently in early stage human testing of its vaccine, but Kuritzkes sees the approach as promising. “As with typhoid and cholera, an oral vaccine makes a lot of sense because you’re trying to stimulate the immune response at the site,” he said.
Fink acknowledged the challenges of antibodies getting to the GI tract and said the company’s actively monitoring that as part of its development process. However, he noted that antibodies are shown to migrate to the GI tract in other experimental norovirus vaccines. Additionally, vaccines with similar technology show that antibodies can migrate: For instance, with Moderna’s Covid-19 vaccine, antibodies are shown to move to sites of infection in the nose.
Moderna dosed its first patient in a global phase 3 clinical trial (usually the last test before seeking regulatory approval) in September of last year. Fink said that testing is expected to include around 25,000 patients and will take about two years. Which means that even if there’s a successful trial, it likely wouldn’t be until 2027 or later that its vaccine hits the market.
Until then, Kuritzkes said it’s important to remember that unlike respiratory viruses, noroviruses are “incredibly hardy” and can survive on surfaces and even withstand hand sanitizer. The best defense against it, he added, is “washing your hands with soap and water,” he added. “Personal hygiene is the most important thing in protecting yourself.”
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