Extremely Low Influenza Rates Challenge Next Season’s Flu Shot

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This year’s flu shot may not work as well as in previous years because plunging influenza levels—ironically due to mask wearing and other steps to tamp down the Covid-19 virus—means there’s a lot less data for picking strains for this fall’s flu season.

Infectious disease professionals say people should still get the shot because any level of protection will lessen the severity of an infection and could keep them out of hospitals and intensive care units. The low infection rates this year also mean the next flu season might sport a similar looking virus, which could help the efficacy of the shot.

Between September 2020 and January 2021, the influenza viruses were detected in just 0.2% of routine throat and nasal swabs. That’s astonishingly low. The average positivity during flu season is 17%, said Rachael Lee, a health-care epidemiologist and an infectious diseases assistant professor at the University of Alabama at Birmingham.

“I cannot recall an influenza season like this in terms of the very low amount of virus circulating,” said Walter Orenstein, an infectious diseases professor at Emory University and director of the Emory-University of Georgia Center of Excellence for Influenza Research and Surveillance.

“There’s been an unprecedented time period in having such low level of flu activity pretty much worldwide,” agreed Richard Ellison, an epidemiologist and infectious disease specialist at the University of Massachusetts Memorial Medical Center.

The World Health Organization had more respiratory samples than ever this year, but they still had very low numbers of influenza virus, Lee said. “I think that makes us question: How strong of data is this? How strong will our flu vaccine be next year? And we really won’t know until we started seeing things open up.”

Extremely Low Influenza Rates Challenge Next Season’s Flu Shot

Mitigation Stops Flu Too

The WHO last month made recommendations on which flu strains to adopt in this season’s shots in the Northern Hemisphere, including a few new strains for both egg and cell-based shots. The Food and Drug Administration’s advisory panel adopted those recommendations.

Vaccine manufacturers such as GlaxoSmithKline and Sanofi rely on those recommendations to make the flu shot. It takes at least six months of lead time to produce enough quantities of a seasonal influenza vaccine, which the Centers for Disease Control and Prevention estimated was anywhere between 194 million to 198 million during last year’s flu season.

“All the mitigation factors” to combat the SARS-Cov-2 virus—masks, social distancing, hand washing—"were coming in at the end of our last flu season,” David Wentworth, director of the WHO’s Collaborating Center for Surveillance, Epidemiology and Control of Influenza, said during the FDA’s vaccine advisory panel’s March 5 meeting. “The percent positivity was way down, and this is real.”

Both the WHO and the CDC have experts who can test what little they have of last season’s flu viruses for levels of transmissibility, which may help in making the judgment, Ornstein said.

“There was still enough circulating influenza to make an informed choice for next year’s vaccine,” Paul Offit, a member of the FDA panel, who’s the director of the Vaccine Education Center at Children’s Hospital of Philadelphia, said in an email.

Public health experts typically look at what’s happening in the Southern Hemisphere to pick the strains for the U.S. and the rest of the Northern Hemisphere. A seasonal flu vaccine reduces the risk of flu illness by 40% to 60%, but only if the strains in the shot match what’s circulating.

“Each year when you’re picking influenza strains it’s an action that has some level of uncertainty,” said Amesh Adalja, a senior scholar at the Johns Hopkins Center for Health Security. “Since what informs selection is the circulation of strains in the prior season, having less information because of an uncharacteristically mild season could make it more difficult to make the correct choice.”

Fewer Mutations

Less influenza circulating also means the virus likely won’t mutate as much as it usually does, and the strains in the forthcoming season could be similar to the last season, both Adalja and Ellison said.

That’s the reason the flu vaccine needs adjustment. “The reason we actually have to change the flu vaccine every year is—just like we’re seeing with Covid, where we have variants showing up— there are variations on a yearly basis in terms of flu,” Ellison said.

The influenza virus each year makes minor changes to the proteins on the surface of the cell so the antibodies developed against last year’s flu typically won’t work as well against this year’s infections.

But such variations are “dependent upon the virus getting into lots of different human beings,” Ellison said. “We don’t know how much change there’s going to be when it’s not circulating very much. It’s an area where we have very little experience when we have such a low amount of circulating virus. It has not happened in a long time.”

Universal Flu Shot

The difficulties highlight the need to develop a universal flu vaccine that can be used year after year, Ornstein said. That requires targeting the body’s immune response against a part of the flu virus that doesn’t change, which takes more time and research. But the investment is well worth it in other areas. Polio and measles vaccines have been effective against mutations for that reason.

“With influenza, the immune response is made against a part of the virus which can mutate,” he said. “That’s why we need to do better than Mother Nature and refocus the immune response on a part of the influenza virus that does not change.”

The first clinical trials to test a universal flu vaccine started about two years ago and are designed to protect against Influenza A, one of the main types of virus responsible for the seasonal flu.

The quest for a vaccine that could protect against multiple strains of influenza has long been a top priority for Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, who said before the pandemic that it would take about 10 years to develop one.

Lee warned that influenza cases could spike as the nation starts to pull back on masking and social distancing as Covid-19 vaccinations ramp up. “Ultimately, as we continue to open up and return to normal, the question will become if we will consider employing some of the lessons learned during the pandemic if we see higher numbers of influenza during the next flu season.”

©2021 Bloomberg L.P.

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