The World Health Organization has recommended dropping a component of many flu vaccines because the viruses it protects against appear to have been driven into extinction in the Covid-19 pandemic.
A family of viruses known as influenza B/Yamagata has not been seen since March 2020, when flu circulation worldwide declined to very low levels in the face of the onslaught of Covid and the protections people took to avoid contracting it. Flu transmission eventually resumed, but of the tens of thousands of influenza B viruses detected and subtyped in the years since, B/Yamagata viruses have not been seen.
“Right now there really isn’t any benefit to having Yamagata in the vaccine,” said David Wentworth, director of the WHO’s Collaborating Centre for the Surveillance, Epidemiology and Control of Influenza at the Centers for Disease Control and Prevention, who was on the expert panel that made the recommendation.
The decision was applauded by influenza virologist Florian Krammer, of Mount Sinai School of Medicine in Manhattan. “Why would you include something that’s not around?” he asked.
The recommendation was made following a weeklong meeting of flu experts from around the world who gather twice a year at the WHO to study circulating flu viruses to advise on what future versions of flu shots should protect against. This week’s meeting was to recommend what viruses should go into the 2024 Southern Hemisphere’s winter shot.
In addition to the fact that there is no benefit to including B/Yamagata viruses in the vaccine at this point, there is a theoretical risk of doing so, a report from the meeting noted. Manufacturers must grow B/Yamagata viruses for inclusion in the vaccines. In most flu shots — the types that are injected — those viruses are killed at a point in the manufacturing process. But a leak from a manufacturing plant could theoretically release B/Yamagata viruses into the world. Likewise, the intranasal flu vaccine FluMist — made by AstraZeneca — contains live but weakened flu viruses. Those viruses, too, could theoretically reintroduce the virus family to the world.
The committee urged regulatory bodies to work with flu vaccine manufacturers to remove the B/Yamagata component from vaccine formulation “as soon as possible.”
“Here we’re balancing the absence of circulation of the B/Yamagata lineage virus with a theoretical risk that we are manufacturing and using a component that’s not necessary,” said Kanta Subbarao, director of the WHO’s Collaborating Centre for Reference and Research on Influenza at the Peter Doherty Institute for Infection and Immunity in Melbourne, Australia.
B/Yamagata viruses haven’t been seen since late March 2020. The rapid and global implementation of social distancing measures, masking, and the profound early reduction in international travel resulted in a substantial reduction in flu transmission. There was virtually no flu season in the winter of 2020-21.
“The other ones — H1, H3, and Victoria — made it through. But there was also a huge bottleneck and Yamagata was not lucky enough to make it through,” said Krammer.
For many low- and middle-income countries, the recommendation will not lead to any change. Many still use trivalent vaccine — a three-in-one shot that protects against influenza A viruses H1N1 and H3N2, plus one of the flu B viruses. In recent years, that would have been the B/Victoria lineage, the only B viruses still circulating.
In countries that moved to quadrivalent flu vaccines a number of years ago, the recommendation may lead to changes in flu vaccine manufacturing, but it won’t be immediate, the experts warned at a press conference the WHO called to announce the outcome of the week’s discussions. Changing the composition of a vaccine requires regulatory approval, which in the case of the United States means signoff from the Food and Drug Administration.
Wentworth said the FDA has been discussing the possibility of recommending removal of the B/Yamagata component from flu vaccines. But whether that’s easy or difficult to do will depend on whether flu vaccine manufacturers still have licenses for former trivalent formulations. STAT reached out to the FDA for comment on the issue, but has not yet heard back.
“Basically it’s going to be different between different companies — whether or not they retained their trivalent license and in which form it was retained, and whether their processes have changed, even though they have their old license,” Wentworth said. “It’s not something that you can do in one day. It’s going to take time. And that’s why our suggestion was to really forecast to the manufacturers and the regulatory authorities that they can start working on this process and try to expedite the process where it makes sense, for safety, etc.”
The experts stressed there is no disadvantage to individuals of getting a quadrivalent vaccine at this point, but no advantage from the B/Yamagata component either.
The flu shots currently used in the United States employ a quadrivalent formulation.
In the years since the Yamagata viruses ceased to be detected, there has been active discussion in the scientific community about replacing that component of quadrivalent shots with another type of flu virus — a second H3N2 vaccine, or one of the bird or swine flu viruses that are seen as pandemic threats. While those ideas are still possibilities, that idea is not yet ready for prime time, Subbarao said.
“From a regulatory standpoint, that’s not very straightforward,” she said. “I think there is a great interest from the influenza research community, but it is still at the research stage rather than being ready for the kinds of discussions that our committee has to make recommendations for the vaccine composition.”