he sole influenza vaccine made in cell culture in the United States may have worked about 20 percent better this flu season than the standard vaccines made in eggs, Food and Drug Administration Commissioner Scott Gottlieb said Thursday.
Gottlieb revealed that figure in a hearing of the congressional subcommittee on oversight and investigations, called to explore this year’s severe flu season and why flu vaccines did not appear to protect especially well.
Gottlieb has said for several weeks that the FDA had data that suggested the cell-culture vaccine performed somewhat better, but this was the first time he publicly quantified the scale of the benefit.
“The data aren’t final yet, but I’m comfortable saying that I think it’s going to be about 20 percent improved efficacy for the cell-based vaccine relative to the egg-based vaccines,” Gottlieb told STAT in an interview after the hearing.
The cell-culture vaccine is sold under the brand name Flucelvax; it is made by Seqirus. It is one of two flu vaccines that are not made in eggs. The other, FluBlok, is made in insect cells; it is made by Sanofi Pasteur. Experts are also eager to see if FluBlok worked better this flu season, but generating that data will be difficult. The vaccine is more expensive than other brands and little of it is used.
Experts have recognized for several years now that growing the viruses used in influenza vaccines in hen’s eggs can cause problems. The viruses have to adapt to grow in eggs; sometimes the mutations they acquire occur at critical locations on the virus. This seems to happen most often with H3N2 viruses, which cause the worst seasonal flu outbreaks.
The effect of those mutations? The H3N2 component of the vaccine trains the recipient’s immune system to be on the lookout for the wrong invaders. Instead of being on guard against a man in a trench coat, the resulting antibodies are looking for a man in a windbreaker.
It’s thought that viruses grown in cell culture don’t acquire as many mutations, so influenza researchers have been eager to see if this vaccine is more effective.
Researchers and public health authorities are also looking for evidence that may come from the military, which used a substantial amount of cell-culture vaccine this flu season. Analysts with the Department of Defense health services are looking to see if there is a discernible difference in infection rates among servicepeople and their dependents who got the cell-culture vaccine.
At the FDA, analysts have been looking at medical records of 16 million people 65 and older covered by Medicare, comparing rates of people who received flu drug prescriptions or who were hospitalized for influenza based on which type of flu shot they received.
Gottlieb said in addition to comparing the egg- and cell-culture-based vaccines, the FDA is looking at whether people who got high-dose vaccines or vaccines with a performance booster known as an adjuvant — both of which types of vaccines are licensed only for seniors —were also afforded more protection.
The study design used by the FDA cannot break down protection by virus type. But because so much of this year’s flu activity has been caused by H3N2, it suggests the benefit mainly relates to that component of the vaccine.
The study design is not identical to the one the Centers for Disease Control and Prevention uses every year to calculate how well the flu vaccine works. So comparing the CDC vaccine effectiveness estimates and the FDA findings is not entirely an apples-to-apples exercise.
Still, the FDA calculations suggest people who got a cell-culture vaccine this year may have gotten modest additional benefit, said Dr. Edward Belongia, of Wisconsin’s Marshfield Clinic. Belongia runs one of the trial sites in the CDC’s flu vaccine effectiveness network.
“If there really is a 20 percent relative effectiveness benefit for cell-culture vaccine versus egg-based, that’s definitely meaningful,” Belongia said. “We’re looking for all the incremental improvements we can get.”
The interim vaccine effectiveness estimates released last month by the CDC suggested that flu vaccines in general had protected about 36 percent of people vaccinated. A 20 percent improvement on that would bring the figure up to 43 percent.
A better comparison, though, might be to look strictly at people aged 65 and older, because that is the group captured in the Medicare data, Belongia said. The interim vaccine effectiveness report said flu shots protected people in that age group about 20 percent of the time. A 20 percent improvement on that would mean about one in four people 65 and older who got the cell culture vaccine were protected, compared to one in five who got a shot made in eggs.
But Belongia cautioned that interpreting the FDA finding is difficult at this point. “Hopefully the FDA analysis will be published soon so we can review the results and compare them with findings from the CDC flu vaccine effectiveness study,” he said.
Infectious diseases expert Michael Osterholm called the 20 percent estimate “a measurable gain,” but insisted better flu vaccines are needed to combat influenza.
“We’ve got to do what we can with what we have. But we can’t be lulled into a false sense of security that what we have is what we need,” said Osterholm, director of the University of Minnesota’s Center for Infectious Diseases Research and Policy and lead author of a 2012 report on influenza vaccine shortcomings and solutions.
Gottlieb noted that it is too soon to say vaccines made in cell culture are the way to go; some years, he told the congressional committee, vaccines made in eggs are more effective.
More study is needed — potentially including a randomized controlled trial comparing the two vaccine types, Gottlieb said. If it appears that the vaccines made in cell culture consistently perform better against H3N2 viruses, that would give the FDA options.
“Maybe we make a recommendation that the H3N2 component has to be produced in a cell-based process and the others can be produced in eggs. There are things that you can do, if you’re able to answer that question, ” he said.
“Right now it’s speculation, it’s hypothesis. I don’t have the answer.”
This story originally miscalculated the impact of the more effective flu vaccine. It has been updated.