Work started this week on next season’s flu vaccine, with experts working off forecasts about which strains of the influenza virus will be making the rounds.
But flu experts are already admitting that most vaccines will give at best mediocre protection, because they’re based on outdated technology.
It’s not a new problem, but one that the slow-moving world of drug and vaccine production seems helpless to improve upon.
“You can’t change on the drop of a dime,” said Scott Hensley of the University of Pennsylvania, an influenza virus expert.
The process of making flu vaccines starts months before the actual flu season gets under way because it takes a long time to make them using the current technology.
A YEARLY COCKTAIL
In February, global flu experts gather to trade notes on what viruses are circulating in different countries and to come to a consensus on which strains the next vaccines should be formulated to target.
Every flu vaccine is a cocktail, aimed at either three or four of the most common flu strains. Flu vaccines must be reformulated every year, because flu viruses mutate constantly in a process called antigenic drift.
In recent years, flu vaccines have been based on H1N1, H3N2 and either one or two strains of influenza B virus. Each of these has a “reference” strain that has particular mutations to match the current drift.
This week, experts at the World Health Organization chose the new reference strains.
These strains are used to make seed virus. Producers inject the seed strains into eggs and incubate them as the virus grows. Then they purify the virus, and either weaken it or kill it to make a vaccine.
Using eggs is a tricky and unpredictable process. Sometimes the virus doesn’t grow well in eggs, which can mean less vaccine than anticipated. And Hensley’s lab identified several mutations that occur when flu viruses are grown in eggs as part of the vaccine-making process.
In fact, the viruses must mutate to grow in eggs, Hensley said. In some cases, the mutations make little difference in the vaccine-making process.
But in recent years, the H3N2 strains have mutated in a way that makes them harder for the human immune system to see. “The egg-adapted strains all have the mutation,” Hensley said.
WHY EGG-BASED VACCINES DON'T WORK WELL
The result is a flu vaccine that doesn’t offer much protection. In part because of the egg mutations, this year’s flu vaccine only has provided about 36 percent protection, the Centers for Disease Control and Prevention estimates. And the vaccine was overall only 25 percent protective against H3N2, meaning it lowered the risk of developing illness serious enough to go see a doctor by 25 percent.
The goal for most vaccines is 90 percent or better protection against illness.
“As long as we have eggs we are going to have this problem,” Hensley said — and other flu vaccine experts agree.
“The only solution is not to depend on eggs,” Hensley said.
There are two flu vaccines on the U.S. market that do not use eggs: Flucelvax, which is grown in canine kidney cells, and FluBlok, which uses an insect virus called a baculovirus grown in caterpillar cells.
One study published last year suggested FluBlok might have worked better than at least one of the other vaccines on the market in past year. But CDC officials say they don’t have enough data to say whether it consistently protects people better, and they do not know enough to recommend one vaccine over another.
'We're hoping this year to find out whether or not there's a performance difference between cell-based vaccines and the egg-based vaccines,' the CDC's Dr. Daniel Jernigan told NBC News.
'Hopefully through our vaccine effectiveness networks we'll get some of that information, but it would be good to see if there is a performance difference between those vaccines.'
Food and Drug Administration Commissioner Dr. Scott Gottlieb said his agency also has some “preliminary” indication that cell-based vaccines might have been more effective during the current season.
“Scientists at the FDA, CDC, and NIH are working diligently to fully understand the basis for this finding, so that all of next year’s vaccines can provide better protection in preventing the flu,” he said in a statement.
“Better understanding why the cell-based vaccine offered better protection against H3N2 this season, when compared to the egg-based vaccine, may offer important clues to help improve the production of a more effective H3N2 vaccine for next season.'
There are other reasons besides eggs that flu vaccines might not work well. The most common circulating viruses might mutate after the WHO chooses its reference strains in February. The mix of what’s circulating might change, also, and the clunky vaccine manufacturing process doesn’t allow for makers to switch gears once they’ve started.
Flu is a major killer. The CDC estimates that between 140,000 and 700,000 people get sick enough from flu every year in the U.S. to need hospital care, and the annual flu epidemic kills anywhere from 12,000 to 56,000 people a year, depending on how bad the flu season is.
The 2017-2018 season has been a severe one, hitting the entire U.S. with widespread influenza activity at once for weeks on end, and killing 97 children so far.
Against this threat, even a lousy flu vaccine is better than no vaccine. “Even an egg-based vaccine is better than nothing,” said Hensley. “Even when you have these mismatches it will not prevent infection but likely prevent disease severity.”
One piece of news for next season’s vaccine: the Advisory Committee on Immunization Practices (ACIP) agreed to once again support the use of FluMist, the only needle-free vaccine on the U.S. market. FluMist is spritzed up the nose and it’s doubly different from other vaccines because it uses a “live” virus – one that is weakened so that it causes a very mild infection to protect against flu.
It’s been off the U.S. market for two years because it inexplicably did not protect people well against the H1N1 virus. Its maker, AstraZeneca subsidiary MedImmune, has tried a different reference strain virus for FluMist’s H1N1 component and says it works better.
In past years, FluMist appeared to work better than injected vaccines in kids, and was recommended as preferred for kids. ACIP said it could not make that recommendation for the coming season as there are no studies to show whether it protects anyone better in a real-life flu epidemic.
All of these troubles mean that the world really just needs a much better flu vaccine.
“Ultimately, developing a universal influenza vaccine that provides protection against many different strains of flu from year-to-year would be ideal,” Gottlieb said.
But don’t look for it next season.
“The reality of such a vaccine is likely to still be several years away,”