In early March, Robert Daum and other infectious-disease experts from around the country will gather in a Silver Spring, Md., hotel to choose the influenza strains that vaccine makers should target for next year’s flu season.
It’s an annual guessing game of sorts, one backed by data but also plagued with uncertainty. And when the guesses don’t exactly match the reality, as happened this past year, it can mean a dismal and deadly flu season.
“We’ll do the best we can,” said Daum, a Chicago doctor who heads the Food and Drug Administration advisory committee that makes the recommendations. But “the virus is smarter than we are at this point. I don’t know of any disease that plagues us more. It’s very, very frustrating and a very inexact science. . . . We do it with varying luck, and I think the luck is mostly the virus’s whim.”
As it does each year, the group will pore over surveillance information from around the globe, hear presentations from government researchers and weigh recommendations from the World Health Organization. The experts will cast their votes for the four specific flu strains — two each from the “A” and “B” types of
the virus — that manufacturers should focus on in making the coming season’s vaccine. Then, they will wait and hope.
Daum said he suspects he’ll leave feeling the way he so often has in the past — head hanging, discouraged, wishing there was a more reliable way to protect people from the yearly scourge of the flu.
Despite constant tracking and surveillance of the virus in labs across the world and the work of hundreds of experts at universities, the WHO and agencies such as the Centers for Disease Control and Prevention, picking the correct flu strains still involves a measure of good fortune. Every few years, experts miss the mark.
“It’s inherently hard,” said Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health. “The one thing the flu is, is unpredictable.”
Global health experts had barely finished making their predictions last year when one of the strains they chose, a virulent type of H3N2 influenza, began to morph. “No sooner than the wheels started turning we started to see a glimpse of a different H3N2 emerging,” Fauci said. This “drift,” as experts call it, rendered this season’s vaccine far less effective than initially expected.
“Even in a good year, the flu vaccine isn’t as good as most of our vaccines. Its efficacy is around the 60, 65 percent range, which is, you might say, passable, but not what we would like,” CDC Director Thomas Frieden said Friday. That rate means that, in a year when the strains closely match the vaccine, about two-thirds of those who get flu shots are far less likely to become so sick that they require a visit to a doctor.
While the agency has not yet published vaccine-effectiveness figures for the current flu season, Frieden said, the numbers are likely to be significantly lower because of the changing nature of the H3N2 virus.
Such viral drift has been a persistent problem over the years, although less devastating than the “antigenic shift” that occasionally occurs, creating an entirely new strain that leaves much of the population defenseless. That’s what led to the 2009 flu pandemic.
Still, in recent days, this flu season has officially crossed into epidemic territory and could prove particularly severe; the CDC said this week that 43 states are experiencing “high or widespread” flu activity, with a growing number of hospitalizations and deaths. And the worst could lie ahead.
A big part of the challenge is timing. Vaccine makers face a constant race to create and churn
out enough doses to distribute throughout the country ahead of the annual flu season.
“It can’t just be done overnight,” said David Greenberg, vice president and chief medical officer at Sanofi Pasteur, which puts out 65 million doses of flu vaccine annually. “It’s a very busy process.”
Every February, the WHO identifies which strains in the Northern Hemisphere are most likely to wreak havoc the following flu season; the FDA’s recommendations, which historically align with the WHO’s, come soon afterward. After that, drugmakers develop formulations for each strain, and regulators ensure that vaccines from numerous manufacturers are safe and similarly potent. “Standardization is critical,” said Jerry Weir, director of the FDA’s Division of Viral Products.
Manufacturers also must produce and package millions of doses and distribute them to physicians offices and pharmacies in time for vaccinations to begin in the fall.
The perpetually tight timeline forces experts to make choices about the next flu season even before the current one has faded. It’s an educated guess, for sure, that includes data about which strains have dominated in recent years and which are picking up in the Southern Hemisphere and likely to migrate north.
But until better predictive models, universal flu vaccines or significantly faster manufacturing processes come along, the element of guesswork remains. So does the frustration when the call turns out wrong.
“Of course, there’s disappointment,” said Gillian Air, a biochemistry professor at the University of Oklahoma Health Sciences Center who has served for the past four years on the FDA’s advisory committee on vaccines. “We’ve done the best we can with the data that’s available. . . . The trouble is, we can’t predict what’s going to happen.”
She and other experts responsible for identifying strains to target as part of the effort to lessen deaths, hospitalizations and general misery caused by the flu each year approach the assignment with a mixture of determination and exasperation: determination to make the best call possible; exasperation at the limitations of battling an ever-changing virus.
Air was there last Feb. 28, when the group met in Building 31 on the FDA’s campus in White Oak, Md. About 3 p.m., after a day of data and presentations and detailed questions about which variations of the flu were likely to strike the United States many months away, it was time to vote on four strains.
“I must marvel at how many human beings are gathered in this room to understand the behavior of a little tiny virus,” said Daum, the Chicago doctor and the committee’s chairman.
“And we don’t get it,” one participant chimed in.
“And we don’t get it,” Daum agreed. “So here we are.”