USA — An experimental vaccine has been shown to elicit antibody responses against all 20 known strains of influenza A and B in animal tests, raising hopes for the development of a universal flu vaccine.

Because influenza viruses are constantly evolving, vaccine developers must keep up with them. The annual flu vaccines that are now available are designed to provide immunity against specific strains that are predicted to circulate each year.

However, researchers occasionally make incorrect predictions, resulting in the vaccine being less effective than it could have been in those years.

Annual flu shots, according to some researchers, could be replaced by a universal flu vaccine that is effective against all flu strains.

The new vaccine, however, offers such broad protection against a range of flu strains that it could even protect against future pandemic strains of influenza.

Researchers have attempted to accomplish this by developing vaccines containing protein fragments shared by multiple influenza strains, but no universal vaccine has yet been approved for widespread use.

Now, Scott Hensley of the University of Pennsylvania and his colleagues have developed a vaccine based on mRNA molecules, following in the footsteps of the Pfizer/BioNTech and Moderna covid-19 vaccines.

mRNA, like DNA, contains genetic codes for protein synthesis. The vaccine contains mRNA molecules that encode protein fragments found in all 20 known strains of influenza A and B viruses, which cause seasonal outbreaks every year.

The strains’ surfaces contain different versions of two proteins that are targeted by immune responses, haemagglutinin (H) and neuraminidase (N).

However, even within a single strain, such as H1N1, these proteins can vary slightly, so the version in the universal vaccine will not exactly match every possible variant.

In mouse tests, the researchers discovered that the animals produced antibodies specific to all 20 strains of the flu virus and that these antibodies remained stable for up to four months.

In another experiment, the researchers administered either the universal flu vaccine or a dummy vaccine containing code for a non-flu protein to mice.

A month later, they infected them with one of two H1N1 flu virus variants, one with an H1 protein that was very similar to the protein in the vaccine, and one with a more distinct version.

All of the mice given the flu vaccine survived infection with the virus with the more similar protein, and 80% survived infection with the more distinct variant.

The mice given the dummy vaccine all died about a week after being infected with either variant.

Another group of mice were given an mRNA vaccine targeted only to the precise flu strain they were exposed to, and all of this group survived over the same time period.

This suggests the universal flu vaccine would offer less protection against new variants of the 20 flu strains than an annual vaccine matched to new forms of the virus, says Albert Osterhaus at the University of Veterinary Medicine Hannover in Germany, who wasn’t involved in the study.

The researchers also tested the universal vaccine in ferrets with similar results.

The mouse and ferret models for influenza are as good as animal models get. The animal data are promising and thus a good indication of what will happen in humans,” says Peter Palese at the Icahn School of Medicine at Mount Sinai in New York.

A key benefit of mRNA vaccines is that they can easily be scaled up compared with other approaches which rely on growing influenza viruses in chicken eggs or in the lab, says Palese

Pandemic risk

The world has already experienced several flu pandemics within the past hundred years or so. During the 1918 flu pandemic, the H1N1 strain infected about 500 million people (a third of the world’s population at the time) and is estimated to have killed at least 50 million.

Since then, there have been three pandemics – H2N2 in 1956, H3N2 in 1968, and H1N1 in 2009.

The 2009 swine flu pandemic – caused by a virus that jumped species to infect humans – was less serious than initially feared.

The threat of another flu pandemic is high, especially from two strains of bird flu —H5N1 and H7N9.

These have been a source of deep concern in recent years as mutations meant that they were able to spillover from poultry into people.

In the case of H7N9, there has also been limited spread among humans, although fortunately this has not been sustained.

This year has seen a record outbreak of the highly contagious H5N1 strain in poultry, with 48 million birds culled in the UK and EU alone, partly because of concerns that it could spread to people.

Estanislao Nistal, a virologist at San Pablo University, said: “All of this implies the potential for an easily and rapidly constructed universal vaccine that could be of great use in the event of a pandemic outbreak of a novel influenza virus.”

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