A global international of an mRNA vaccine against norovirus is getting underway with the aim of reducing the health burden caused by the infamous “winter vomiting” bug. The trial has been complicated by the emergence of a new norovirus strain that is causing soaring numbers of cases in parts of the world, including England.
“Unfortunately, one of the strains which is most prevalent isn’t in that jab,” says Patrick Moore at the UK’s National Institute for Health and Care Research, who is leading the UK branch of the trial. “The high cases are probably down to that variant rather than the variants that we’re hopefully protecting against.”
However, it is possible that the vaccine will provide some protection against the new variant, and the trial will still reveal if it is effective against the three variants it does include.
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Norovirus is a highly contagious virus that causes inflammation of the stomach lining and intestines, or gastroenteritis, leading to vomiting and diarrhoea. An individual can be infected by as few as 10 viral particles and go on to shed enough viruses that they could theoretically infect the entire world population, says Moore.
Deaths are very rare where people get good care, but vulnerable people – mainly the very old or very young – may end up in hospital, so the virus causes a huge burden on healthcare systems.
“We have 12,000 hospital admissions in England alone, and that’s a cost to the NHS of £100 million,” says Moore. “If you include loss of productivity, it’s £300 million.”
Hence the need for a vaccine. There have been many attempts to develop one but none has yet been approved. One of the key problems is that the norovirus is so varied. Based on the characteristics of key genes, it is divided into 10 genogroups, such as GI or GII, each of which is further divided into up to 49 genotypes, such as GII.4 or GII.17, and there are further variations within genotypes.
Normal vaccines consist of whole viruses or viral proteins, which are expensive to make. mRNA vaccines instead contain instructions for producing viral proteins, making it easier and cheaper to create vaccines that target multiple variants. “With the mRNA technology, you’re using the mechanisms within our own bodies to help,” says Moore.
The experimental mRNA vaccine, developed by Moderna, contains mRNAs coding for the main outer protein of three norovirus variants: GII.4, GI.3 and GII.3. Until recently, these were the most common variants circulating globally.
However, over the past year, a new GII.17 variant has become common in Europe and North America. Some media reports wrongly call it the “Kawasaki variant”, which applies to a different variant of GII.17.
In the UK, the new GII.17 variant is responsible for around 60 per cent of cases. The number of lab-confirmed cases of norovirus in England is over the previous five years for this time of year.
Fortunately, the plan was always to test trial participants who develop norovirus to identify which genotype they are infected with, says Moore. This means the trial will be able to reveal if the vaccine has any effect against the circulating genotypes.
In previous trials, vaccines against one genotype have sometimes reduced the severity of illness caused by another genotype, says at Baylor College of Medicine in Houston, Texas. But as long as it works against GII.4, it could still make a big difference, he says, as GII.4 variants have caused more than half of all cases over the past decades.
In this event, the vaccine would probably be altered to include GII.17 in the future, says Moore. “One of the benefits of mRNA vaccine technology is that it can be updated quite quickly.”
Another question is how long protection will last. People may need to be revaccinated regularly as immunity fades or new variants emerge, similar to flu vaccines.
Apart from the emergence of GII.17, the trial is going “amazingly well”, says Moore. “In the UK, we’re well on target to hit the number of recruits that we’re aiming for.” Only volunteers over the age of 70 are still required.
Other branches of the trial are underway in the US, Canada and Japan, and it will be extended to more countries in 2025.
Participants in the trial are injected with either the vaccine or a placebo, and then followed to see if they develop norovirus. Every so often, the data will be reviewed to see if those given the vaccine are proving less likely to get infected or become severely ill than those given the placebo.
Getting clear results could take a year or so. Normally, having higher levels of norovirus in circulation would produce results sooner, but because GII.17 isn’t in the vaccine, this may not be the case. If the results are good, the trial could be extended to include children, says Moore.
If the mRNA vaccine is approved, health authorities will then consider how cost effective it is. “The question of being worthwhile is likely an economic question and will depend on the target population: what is the vaccine going to cost and what savings will preventing gastroenteritis yield?” says Atmar.
