By Jasmin Singh
Today, in a hotel ballroom on the outskirts of Washington, D.C., the defenses against next year’s flu season are being decided.
That’s where the Food and Drug Administration’s Vaccines and Related Biological Products Advisory Committee is meeting to choose the vaccine antigens to be used in next season’s flu shot. Last week, World Health Organization officials made their recommendation for next year’s influenza vaccines for the northern hemisphere.
The meeting’s goal: to create one vaccine that covers four influenza strains for the upcoming season, according to Robert Daum, chair of the committee, a pediatrics professor at the University of Chicago and an expert in infectious diseases.
“We look at the circulating viruses this year, whether they’ve changed or not from before,” Daum said. “Of course, they will have.”
That’s what happened this past year. The vaccine chosen at the VRBPAC meeting in 2014 turned out to be not very effective. And that’s led to a record number of deaths attributed to the flu in North Carolina and a high number in the U.S. as a whole.
Since the first week of October, North Carolina has seen 176 flu-associated deaths. In the same time period last year, there were only 107.
Evolution in action
This year’s vaccine includes an H1N1 strain, an H3N2 strain and two B viral strains. But the strain experts thought would be predominant wasn’t.
Daum said that though the predominate strain circulating this year is H3N2, which is included in the vaccine, it is an antigentic drifted strain.
Daum explained that “antigenic drift” is what happens when a minor change makes this year’s virus different enough to not respond to antibodies created in response to this year’s vaccine.
“The virus is smart too,” Daum said. “I often think that it’s listening in to our discussions in March and it hears that we’re going to pick a vaccine that’s going to target it for next year, and it says, ‘Hmm, I’ve got to change myself or I’m going to be killed by this year’s vaccine.’”
When they formulated this year’s vaccine last spring, experts thought the H1N1 strain would be this year’s predominant flu. But in the end, few of those H1N1 viruses circulated, and the B viruses weren’t very prevalent either. The H3N2, being wily, drifted, and that transformed virus really got around. Because people who got the vaccine didn’t get much protection against the H3N2 strain, it made a lot of people sick this winter.
A study by the Centers for Disease Control and Prevention showed the current vaccine was only about 23 percent effective at arresting the disease in patients. Usually, the effectiveness is more like 60 percent.
“The [H3N2] virus basically evolved under the impression of the immune system of people all over the world, said David Spiro, section chief of DMID’s Respiratory Diseases Branch at the National Institutes of Health. He said that means, essentially, a new virus evolved out of the old viruses that were circulating.
Spiro said the committee must make its decisions six months in advance, and that gives the virus enough time to change.
“This is really Darwinian selection in action,” he said. “It’s natural selection in people based upon immune systems and the virus’ ability to evolve. You have humans taking their best guess and nature outsmarting them.”
“As a result, [this year] we really have a vaccine that doesn’t have a very high effectiveness,” Daum said.
Seniors at risk
Spiro said though healthy individuals might experience many common symptoms of flu, it’s the vulnerable populations for whom the flu can be deadly.
“The flu can cause death by respiratory distress or it can cause a weakening of the immune system in such a way that a secondary bacterial infection can cause pneumonia and kill,” he said. “That’s a more common form of death for the elderly.”
“This was legitimately a lot of severe illness among seniors, people over 65,” said Zack Moore, an epidemiologist with the state Department of Health and Human Services.
“The CDC has a national hospitalization system that showed that the hospitalization for seniors was really high,” said Moore, who noted there were outbreaks in nursing homes and adult care homes in North Carolina. “It was a really, really tough year for those over 65, in part related to the strain.”
He also said the high numbers this year could be, in part, a function of increased awareness of the need to report.
“There’s been a lot of attention over the past few years and encouragement to report and test, so it’s a little bit self-fulfilling; people consider flu and test for it more,” Moore said. North Carolina has had an electronic reporting system in place for adult flu deaths since 2009.
And even though 176 people seems high, Moore said there will be many more, but that most of the deaths from flu won’t get attributed to the virus.
“We really use the flu-death numbers as a rough estimate of who’s being hit the hardest,” he said. And the state surveillance numbers help experts estimate how many people in the U.S. will die as a result of the flu. This year, the estimate is for about 26,000 deaths.
“Say you have an 86-year-old in a nursing home who has other conditions, and they get a respiratory disease. They might not get as aggressive a diagnostic workup,” Moore said. That person might die from pneumonia that developed as a result of the flu, but the flu diagnosis never was confirmed. These deaths might end up labeled as “flu-associated” because doctors have a difficult time establishing the actual cause of death.
And then there are limitations to the flu test itself.
“A rapid flu test misses about half the cases,” Moore said.
Formulating next year’s shot
Once the committee makes an estimated guess on what flu strains will circulate next year, vaccine manufacturers begin to collect serum grown in eggs to start the vaccine process.
“Some manufacturers make a recombinant virus, or they combine it with their vaccine strain and they grow those viruses to make a live, attenuated vaccine, or the flu mist,” said Brendan Flannery, an epidemiologist with the influenza division at the CDC . “Other manufacturers split the virus or inactivate the virus and they make what we call the inactivated vaccine.”
The majority of vaccines are of this second type.
According to Flannery, some vaccines are also grown in cells instead of eggs.
“For this year’s vaccine, they will probably recommend something that is close to what is circulating this year,” he said.
Flannery said the final vaccine is usually available after six months, around August or September.
“That’s a very tight timeline, from indicating what’s going to be in the vaccine to growing it, preparing it and then having the vaccines distributed on time,” he said.
Daum said the industry needs a better vaccine.
“It would be nice to have a vaccine that you didn’t have to give every year,” he said. “One that’s more broadly protective against different shifts and different drifts.
“There is a lot of room for a new kind of flu vaccine, but we don’t have one yet.”