Last year’s seasonal flu vaccine effectiveness was just 42%, the US Centers for Disease Control and Prevention estimated. Even if vaccinated, then, people had inadequate protection against the flu.
This limited effectiveness was due to a mutation that occurred in the influenza A (H3N2) vaccine strain, according to a new study published Monday in the journal Proceedings of the National Academy of Sciences. This vaccine mutation resulted from an egg-based manufacturing process commonly used today.
This year’s flu vaccine may also be imperfect, said Scott Hensley, author of the new study and an associate professor at the University of Pennsylvania. Add to that, he said, “this could end up being a pretty bad flu season.”
Still, he said, “our best protection” against severe illness is getting vaccinated with the flu shot we have today.
Each year before flu season begins, a vaccine is made based on whichever virus strains are expected to circulate. The selected seed strains are distributed to vaccine manufacturers which then produce their formulations and make them available to health care professionals before the season begins.
During the 2015-16 season, vaccine effectiveness was 47%, while for the previous 2014-15 season, effectiveness was just 19%, according to the CDC. While the overall effectiveness of last season’s vaccine was 42%, it was only 34% effective against the H3N2 viruses that dominated the season.
Vaccine effectiveness varies based on how well it matches the circulating virus strains. Sometimes, a vaccine corresponds to the predominant virus yet its effectiveness is still not what scientists would expect. Trying to understand which element of the vaccine failed is difficult.
Hensley and his team began their investigation of last year’s vaccine by looking at the seed strains that had been distributed to vaccine manufacturers. These seed strains had been propagated in chicken eggs, the common method used today.
“The sequences of these viruses are available and when we did an alignment to see what the sequence of these vaccines were compared to the viruses that were circulating, it became very obvious that there was this mutation,” said Hensley.
To see the effects of the mutation, the team next looked at how the immune systems of both animals and humans who’d been inoculated with an egg-based flu vaccine responded to the actual circulating viruses.
The antibodies — immune system proteins that fight invading pathogens — elicited in both animals and humans failed to bind to and neutralize the flu viruses, Hensley and his colleagues found.
While most vaccines in the United States are made in chicken eggs, a small fraction are produced in insects or mammalian cells, Hensley explained. (These are given to people with egg allergies.) He and his team compared immune responses in animals and humans who had received a cell-based vaccine — in this case, Flublok made by Protein Sciences Corporation.
“And we found both animals and humans receiving that (cell-based) vaccine had superior antibody responses that could bind and neutralize these circulating H3N2 strains,” said Hensley.
Making a better vaccine
“Most of the infrastructure to produce vaccines in the US is based on chicken eggs,” said Hensley. There are good reasons for this, including the fact that egg-based propagation allows manufacturers to quickly produce large quantities of vaccine.
While egg adaptations have always been a problem, beginning last year it had become a “huge problem,” said Hensley. “As soon as you try to grow this virus in eggs, within a few hours, the virus will acquire this kind of mutation.”
This is not an easy problem to fix, he said. To produce vaccines in cells means “a very expensive process for companies to just change their overall manufacturing process,” Hensley explained. “You can’t really do that on the drop of a dime.”
Meanwhile, the same seed strains used last year are being used this year to make the current vaccine, said Hensley.
“This year may be especially difficult because, in addition to this egg adaptive mutation which was present last year, there’s indication that the H3N2 viruses are actually evolving,” said Hensley.
Not only will the vaccine be a mismatch with the actual circulating viruses due to egg adaptation but the vaccine could also be a mismatch due to unexpected viral evolution.
What kind of flu season is ahead?
It’s too early to speculate which viruses will become dominant in the United States over the course of the coming flu season, said Hensley, “but it’s starting to look like it will be H3 viruses.” H3 viruses are influenza A viruses.
“There are the A group of viruses and the B groups,” said Dr. William Schaffner, an infectious disease specialist at Vanderbilt University. “The A groups are the ones that usually are responsible for large epidemics … whereas the B flu strains usually smolder along. They always cause illness — it can be just as severe as the A strains — but they don’t produce large outbreaks.”
Though last year’s vaccine was mostly ineffective in thwarting the flu, it still prevented nearly 30% of hospitalizations that might have resulted, according to CDC calculations. For older adults, that rate was even higher, at 37%. Plus, the vaccine reduced outpatient visits by 42% last season.
The CDC advises everyone 6 months and older to get a flu shot, as only injectable flu vaccines are recommended. More than 130 million doses of flu vaccine have been distributed so far this year and flu activity is still low across the nation.
It’s still early days, but experts believe we may be facing a tough season, and not only because of vaccine concerns.
Australia had a tough flu season this year, with a total of 215,280 laboratory-confirmed cases and 504 flu-associated deaths reported to its National Notifiable Diseases Surveillance System as of October 13, government data show. According to a surveillance system report, adults over the age of 80 and children between 5 and 9 years old have been most affected.
“In general, we get in our season what the Southern Hemisphere got in the season immediately preceding us,” Dr. Anthony Fauci, director of the United States’ National Institute of Allergy and Infectious Diseases, said in an interview last month.
An “intelligent guess,” therefore, is that the Northern Hemisphere, like the Southern Hemisphere, will likely battle more cases of the viral infection, he said, though “with influenza, it is never 100%.”
“If H3N2 viruses dominate the US flu season again this year, vaccine effectiveness will likely be moderate to low again,” said Hensley.
Still, he said, everyone should get their annual flu shot.
“The other components of the vaccine, like H1N1 and influenza B, will likely provide excellent protection,” said Hensley. “The vaccine will also likely prevent severe disease and death caused by H3N2 viruses, even though this component of the vaccine is mismatched.”