A new flu vaccine might be able to ward off all strains of this complex, rapidly mutating disease.
A new study in mice finds that, by presenting a cocktail of flu proteins to the immune system, researchers can induce immunity to strains that the animal has never encountered. Though scientists still have to test whether the vaccine is safe and effective in humans — clinical trials could begin in about a year — they hope the vaccine could prevent both seasonal flu and future flu pandemics.
"We think this is a very simple, practical, straightforward approach to trying to make a vaccine that might offer broad protection in humans," said study researcher Jeff Taubenberger, a pathologist and infectious-disease specialist at the National Institute of Allergy and Infectious Diseases (NIAID). [7 Devastating Infectious Diseases]
The challenge of influenza
Most vaccines work by presenting the immune system with either weakened pathogens, or pieces of pathogens that trigger the production of antibodies to the disease.
But the flu is a tough nut to crack. The envelope surrounding the virus's genetic material is studded with two major types of proteins: hemagglutinins, or H proteins; and neuraminidases, or N proteins. The typical flu monikers, such as H1N1, reflect which type of proteins that flu virus sports.
There are 18 different H protein subtypes, 16 of which are found in birds, the main source of new flu strains, Taubenberger said. And there are nine different N protein subtypes.
"If one host is infected with two different strains of virus at the same time, the virus can mix and match its genes to make new combinations" of these subtypes, Taubenberger said — in other words, 144 varieties of fever, chills, nausea and fatigue.
On top of that complication, flu viruses also mutate very quickly, which means they can evade the immunity from a slightly out-of-date vaccine or a previous infection that should impart immunity, since a person's body will already have the matching antibodies. These factors explain why the seasonal flu vaccine changes every year, and why that vaccine is not always effective, Taubenberger said. The 2015 flu shot was an example of a vaccine that didn't work as well as hoped because of changes to the dominant flu strain's genetic code.
Flu cocktail
Taubenberger and his team created a mix of noninfectious flulike particles containing four of the 16 common H proteins: H1, H3, H5 and H7. They chose these proteins because most human influenzas are caused by H1 and H3 strains, and because H5 and H7 outbreaks among birds have infected humans, threatening to cause pandemics.
In addition, both H1 and H5 are in one subfamily of proteins, Taubenberger said, while H3 and H7 represent the other half of the flu "family tree."
The researchers spritzed the mix up the noses of mice, and followed with a booster three weeks later. A control group of mice got a snort of saltwater. After another six to eight weeks, the mice were infected with real flu viruses.
"What we got was really kind of unexpected and kind of remarkable," Taubenberger said. "We were able to provide really broad protection against a wide variety of influenza viruses, but most importantly, against viruses that expressed H subtypes that weren't in the vaccine at all."
Overall, about 95 percent of the mice were protected against the eight strains of flu tested, the researchers report today (July 21) in the open-access journal mBio. This level of protection was so surprising that the researchers aren't quite sure how it even works. Unlike in other vaccines, it seems that the antibody response is not the main reason the new spray works, Taubenberger said. T cells, a type of white blood cell, might be playing a role, he said.
The researchers are now investigating how the vaccine works. They're also testing it in ferrets, which are the animals most often used to mimic how humans catch and resist the flu. If those tests show promising results, human safety trials for the new vaccine could begin next year, with clinical trials for effectiveness starting the year after that, Taubenberger said.
The new vaccine is one of several attempts funded by the National Institutes of Health to create a universal flu vaccine.
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