Bird Flu Fears Stoke the Race for an mRNA Flu Vaccine

Researchers have been working on mRNA flu vaccines since before the Covid-19 pandemic, but we may get one for bird flu first.

Unsettling news emerged from Missouri in late September. Six health care workers in the state developed mild respiratory symptoms after caring for a somewhat high-profile patient—the first person to have caught bird flu despite having no known contact with infected animals. The fear was that the virus could be spreading from person to person.

The Centers for Disease Control and Prevention emphasize that so far only the original patient has tested positive for bird flu, however; one of the workers has tested negative for the virus, while the others were not tested and have provided blood samples for further analysis.

This kind of bird flu is caused by the H5N1 virus, one of many subtypes of influenza A, the most common type of flu virus known to infect people. H5N1 has circulated in birds and some other animal populations for years but has only occasionally caused small outbreaks in humans. The concern is that this could change. H5N1 is constantly evolving and might be getting better at transmitting between humans. Since the vast majority of people have no immunity to this particular flu virus, some worry that it could cause the next pandemic.

“So far, it doesn’t seem like it’s widespread in humans,” says Gabrielle Scher, a postdoctoral researcher at the University of Pennsylvania. “On the chance that [that changes], we need to be ready.”

Scher and her colleagues are working on messenger RNA vaccines for bird flu. A revelation during the Covid-19 pandemic, mRNA jabs can be manufactured very quickly, which is useful in a pandemic scenario. They work by depositing short pieces of RNA—molecules that carry genetic information—into your body. These snippets of genetic code prompt your immune system to replicate—for example—part of a virus encoded by that mRNA and then learn how to fight it off. With the Covid vaccines, those instructions targeted a key part of the coronavirus’ outer structure, the spike protein.

Scher has seen for herself what happens when an mRNA bird flu vaccine is put to work. She has watched a lab instrument detect tiny amounts of fluorescence as antibodies in blood from vaccinated mice bind to H5N1 proteins—like tiny countermeasures neutralizing an incoming missile. She and her colleagues published the results of their work on an H5N1 vaccine tested in animals earlier this year and are now working toward human trials.

Scientists have been developing mRNA influenza vaccines since before the pandemic. Drug companies such as Moderna, Pfizer, and GSK are working on mRNA jabs that would target various different flu strains responsible for regular seasonal outbreaks; all three are also separately developing bird flu vaccines.

But clinical trials have yielded some mixed results. Last year, Moderna reported that a trial of one of its mRNA flu vaccines showed good results against strains of influenza A but insufficient efficacy against strains of influenza B, the second most common type of flu. Pfizer has had similar problems, according to brief reports about one of its mRNA flu vaccines that emerged in August; a spokesperson says the company is analyzing the full data from the study. GSK has also grappled with efficacy against influenza B but last month reported improved success of its mRNA flu candidate against B strains, following adjustments.

It isn’t necessarily obvious what part of a flu virus any potential mRNA vaccine should aim for. “You need to make sure you’re targeting the right part of the virus,” says Scher. With Covid-19, the prominent spike protein fit the bill. But influenza viruses are arguably more complicated and mutate more quickly, meaning that if you pick the wrong protein, your jab could prove less effective than hoped. The flip side, Scher suggests, is that mRNA vaccines could make it possible to target multiple proteins or parts of proteins on the same virus—a multipronged strategy.

And while they’re tricky to develop, the speed with which mRNA vaccines can be produced could be hugely beneficial. Traditionally, flu vaccines contain inactivated viruses that are grown in hens’ eggs. This works reasonably well, but it takes a long time to make such jabs, which means health authorities have to publish their predictions about which strains of flu will be circulating during the upcoming winter well in advance. If you could manufacture vaccines more quickly, you could make more accurate predictions nearer to flu season.

Not only that, researchers hope that a single mRNA shot could one day target 20 or more strains of flu at once, relieving the need for some of this guesswork. Scher’s colleagues are working on such a “universal” flu vaccine.

With clinical trials ongoing, it’s still early days. Sheena Cruickshank, an immunologist at the University of Manchester, has watched reports about emerging mRNA flu jabs with interest but says that questions remain. “We don’t yet know how long-lasting the immunity they produce is,” she says.

Michael Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota, concurs, though he notes that all flu jabs, regardless of how they are made, have a waning immunity problem—your protection could decline by around 10 percent every month following injection.

A concern specific to mRNA vaccines is that they tend to cost more than traditional flu vaccines and must be kept refrigerated, which may make them difficult to roll out in areas with poor infrastructure. Researchers are also concerned that they may meet with more vaccine hesitancy. “The mRNA vaccine platform, per se, is probably the one that seems to get the most misinformation,” notes Cruickshank. “That could be a disadvantage.”

A new wave of mRNA flu vaccines could be particularly impactful for older patients, says Jenna Bartley, an assistant professor at UConn Health, a health research center and hospital. Older people are among the most at risk from flu, but current vaccines are less effective in higher age groups, as their immune response tends to be weaker. mRNA Covid-19 jabs, however, have proven effective in older people as well as younger people.

It may be some time before mRNA jabs are available for seasonal flu. However, if H5N1 starts infecting a lot more people, and especially if we find that it is transmitting frequently between humans, there’s a chance that an mRNA bird flu vaccine could be the first such jab rolled out on a wide scale. US health officials have said that an mRNA H5N1 vaccine could be made available within weeks, if required.

Osterholm agrees that such a timeframe is realistic. The real challenge, he points out, would be getting any new H5N1 vaccine to the people who most need it. Covid-19 jabs emerged in wealthy countries and were delivered to people very quickly, he says, but “for much of the world, that wasn’t the case at all.”

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