mRNA can deliver universal flu vaccine, say US researchers

Scientists in the US say they have developed an mRNA-based vaccine that encompasses all 20 known subtypes of influenza that could form the basis of a future universal jab.

While the shot is still in preclinical development, if it works in human trials it could raise the prospect of eventually sidestepping the annual scramble to guess the most likely strains to be circulating in the following flu season, and protect against future flu pandemics.

Animal testing of the vaccine by the team at the University of Pennsylvania’s Perelman School of Medicine – published in the journal Science – has shown that it provides broad protection from otherwise lethal flu strains, dramatically reducing signs of illness and death.

A universal flu vaccine could help avoid the variability in effectiveness seen with current seasonal jabs, which is generally around 60%, but can fall to as low as 10% if health authorities and manufacturers incorrectly guess the strains that end up spreading in the flu season. They would also likely provide little protection against an emerging, pandemic variant.

“The idea here is to have a vaccine that will give people a baseline level of immune memory to diverse flu strains, so that there will be far less disease and death when the next flu pandemic occurs,” said lead author Scott Hensley, a professor of microbiology at UPenn.

While there is a long way to go before the vaccine may be ready for widespread use, the mRNA technology behind it – deployed so rapidly and effectively against COVID-19 – makes the team hopeful that it could progress quickly through development.

The goals of the programme are also similar to those in COVID vaccine development. Rather than completely preventing infections, the aim would be to stimulate a memory immune response that could be quickly recalled and adapted to new pandemic viral strains.

“It would be comparable to first-generation SARS-CoV-2 mRNA vaccines, which were targeted to the original Wuhan strain of the coronavirus,” said Hensley. “Against later variants such as Omicron, these original vaccines did not fully block viral infections, but they continue to provide durable protection against severe disease and death.”

Their vaccine is based on 20 versions of the haemagglutinin antigens of type A and B influenza viruses, which were shown in mice and ferret models to induce a strong antibody-mediated response against different flu subtypes. That included viruses that were significantly different from those included in the shot.

Earlier efforts to develop a universal flu vaccine have been mainly aimed at uncovering core protein antigens that are conserved between different strains, but that has proved to be a challenge.

Sounding a note of caution, Raúl Ortiz de Lejarazu y Leonardo, director emeritus of the National Influenza Centre in Valladolid, Spain, warned against premature excitement about these early studies.

While the study is “well-conceived and comprehensively conducted”, he said, “there is a long, sometimes insurmountable, way to go from the animal model to humans. The type of response, the extent of the response, the persistence, etc., are not similar.”

Hensley et al say they are currently designing human clinical trials of the vaccine candidate. Meanwhile, mRNA vaccine heavyweights Pfizer/BioNTech and Moderna are also working on novel shots for flu, although they are initially focusing their efforts on multivalent seasonal shots targeting a limited number of strains.

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