“There is one certainty: there will be another flu pandemic in the future,” an expert warns

The influenza epidemic across the WHO European Region has returned to baseline levels, with cases recently dropping beneath the seasonal threshold for the first time since early December. While this alleviates immediate pressure on the Region's health systems from influenza, preparations are ongoing for the next flu season, and experts are vigilant about a virus of pandemic potential.

Nicola Lewis, Director of the Worldwide Influenza Centre at the Francis Crick Institute in London, United Kingdom, is frank about the risks flu poses: "I think the chances that disease X will be an influenza virus are probably greater than for any other known pathogen group that I can think of," she says. Disease X is a term used to describe a hypothetical novel or unknown disease that could cause another pandemic.

The Francis Crick Institute is one of 7 WHO collaborating centres responsible for analysing influenza viruses circulating in the human population. They characterize flu strains and use this information to inform risk assessment and vaccine development, both for seasonal influenza and for strains with pandemic potential.

The Institute is part of the WHO Global Influenza Surveillance and Response System (GISRS), which consists of over 150 laboratories and institutions worldwide.

Adapting vaccines to changes in seasonal influenza

Currently, annual epidemics of seasonal influenza cause up to 650 000 deaths globally; as many as 72 000 - about 11% - of these occur in the Region, mainly among people at higher risk of severe disease, including older people, those with chronic heart or lung diseases, children under the age of 5 years and pregnant women. The seasonal flu vaccine is a safe and effective way to reduce the severity of infections.

To tailor the vaccine to circulating variants, twice a year WHO organizes consultations with an advisory group of experts gathered from WHO collaborating centres and WHO Essential Regulatory Laboratories that analyse influenza virus surveillance data generated by GISRS. The recommendations issued are used by national vaccine regulatory agencies and pharmaceutical companies to develop, produce and license influenza vaccines for the following influenza season.

Since the influenza season coincides with the autumn/winter season in the northern hemisphere, and manufacture and distribution take time, the Composition of Influenza Virus Vaccines recommendation meeting is organized in February. "The recommendation meeting is at the end of a very long effort undertaken by the GISRS network, made up of 151 national influenza centres in over 129 Member States," says Nicola.

"The national influenza centres take receipt of clinical specimens that are positive for influenza viruses, and they start the process of analysing them," she explains. "Then they share these specimens with the 7 WHO collaborating centres, including the one in London, who then take up the baton to analyse the genetic sequences and the antigenic properties of these viruses (the immune response in individuals)."

The WHO collaborating centres take this information to the recommendation meeting where they spend a week examining the data presented before advising on the human seasonal influenza strains that should be countered through tailored vaccine production.

"Flu changes constantly and our job as collaborating centres, underpinned by the huge amount of work done by the national influenza centres, is to make sure that we understand how the viruses are evolving. The seasonal flu vaccine is an essential part of our armoury in helping to protect the human population."

Influenza spillover from animals

At the Composition of Influenza Virus Vaccines recommendation meetings, experts also analyse viruses that are circulating in animal populations to prepare candidate vaccine viruses that could become a crucial countermeasure in the face of another pandemic.

"One of the aspects of flu that is fascinating is that it is continuously evolving, which means that it's able to escape prior immunity that we might have to a particular flu virus," says Nicola.

"Flu viruses can also undergo what we call re-assortment, which happens when 2 different flu viruses infect a person or infect a pig at the same time. They shuffle their genetic material so that the progeny flu virus that comes out of the pig or the human is actually different."

Pigs represent the ideal mixing vessel in which flu can mutate, since they can catch influenza from birds and humans. Periodically, viruses from specific animal populations spill over into other animal populations, or into humans, where they can cause severe damage. They sometimes cause single infections, but they have the potential to cause a pandemic.

Preparing for a potential pandemic

Highly pathogenic avian influenza is on the radar due to its recent rapid evolution and its ongoing detection in cattle in the United States of America. It is often lethal to domestic poultry, but so far not easily transmissible to humans. Since 2020, strains of the virus have spread globally through wild bird hosts - throughout Eurasia as well as into Africa, North and South America, and even Antarctica.

As well as killing many millions of wild and domesticated birds, including poultry raised for human consumption, highly pathogenic avian influenza has also shown itself to be transmissible and dangerous to mammals such as tigers, foxes, mink and fur seals. Infections in mammals are particularly concerning because they can create the potential for mutations that increase the risk of mammal-to-mammal spread and transmission to or among humans.

"We have never seen this kind of situation with a highly pathogenic H5 virus before. I certainly think that if you'd asked me in 2019, this would not have been the picture I would have conjured up in my mind about what bird flu could do," Nicola notes.

Researchers at the Worldwide Influenza Centre at the Francis Crick Institute are committed to understanding these evolutionary changes to support global preparedness efforts for a potential pandemic from flu viruses.

Nicola stresses that frameworks such as GISRS, so critical to global pandemic preparedness, are dependent on trusting, collaborative partnerships and the sharing of near real-time information. She urges Member States currently negotiating the Pandemic Accord ahead of the 77th World Health Assembly to work together for the benefit of all.

"My message to international communities is that we have to set aside our reticence. We have to set aside our parochial concerns and remember the impacts and the devastating consequences of a global pandemic from whatever disease agent it comes from."

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