They develop a vaccine for the 20 known flu subtypes

A new experimental mRNA-based vaccine against all 20 known flu virus subtypes provided broad protection against otherwise lethal flu strains in initial testing, so it could one day serve as a measure general preventive against future influenza pandemics, as published by researchers from the Perelman School of Medicine at the University of Pennsylvania (United States), in the journal ‘Science’.

The “multivalent” vaccine uses the same messenger ribonucleic acid (mRNA) technology used in Pfizer and Moderna’s SARS-CoV-2 vaccines. This mRNA technology that enabled those covid-19 vaccines was pioneered at Penn. Tests in animal models showed that the vaccine dramatically reduced signs of disease and protected against death, even when the animals were exposed to different flu strains than those used in the vaccine’s manufacture.

“The idea is to have a vaccine that gives people a basic level of immune memory against various strains of flu, so that there will be much less illness and death when the next flu pandemic hits,” explains the lead author. of the study, Dr. Scott Hensley, Professor of Microbiology at the Perelman School of Medicine.

Hensley and his lab collaborated on the study with the lab of mRNA vaccine pioneer Dr. Drew Weissman, Roberts Family Chair in Vaccine Research and Director of Vaccine Research at Penn Medicine.

Influenza viruses periodically cause pandemics with huge death tolls. The best known was the “Spanish flu” pandemic of 1918-19, which killed at least tens of millions of people worldwide. Influenza viruses can circulate in birds, pigs and other animals, and pandemics can start when one of these strains jumps to humans and acquires mutations that make it better suited to spread among humans. Current flu vaccines are simply “seasonal” vaccines that protect against recently circulating strains, but are not expected to protect against new pandemic strains.

The strategy used by the Penn Medicine researchers is to vaccinate using immunogens – a type of antigen that stimulates the immune response – of all known influenza subtypes to obtain broad protection. The vaccine is not expected to provide “sterilizing” immunity that completely prevents viral infections. Instead, the new study shows that the vaccine elicits a memory immune response that can quickly recover and adapt to new pandemic viral strains, significantly reducing severe illness and death from infections.

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

The experimental vaccine, when injected and absorbed by recipient cells, begins to produce copies of a key influenza virus protein, the hemagglutinin protein, for all twenty hemagglutinin subtypes of influenza: H1 through H18 for for influenza A viruses, and two more for influenza B viruses. “For a conventional vaccine, immunizing against all of these subtypes would be very challenging, but with mRNA technology it’s relatively easy,” Hensley says.

In mice, the mRNA vaccine elicited high levels of antibodies, which remained elevated for at least four months, and reacted strongly to all 20 influenza subtypes. In addition, the vaccine seemed relatively unaffected by previous exposures to the flu virus, which can skew immune responses to conventional flu vaccines. The researchers found that the antibody response in the mice was strong and widespread, regardless of whether the animals had been previously exposed to the flu virus.

Hensley and his colleagues are currently designing human clinical trials, he said. The researchers envision that, if these trials are successful, the vaccine may be useful in eliciting long-term immune memory against all influenza subtypes in people of all age groups, including young children.

“We think this vaccine could significantly reduce the chances of getting a serious influenza infection,” Hensley says, adding that in principle the same multivalent mRNA strategy can be used for other viruses with pandemic potential, including coronaviruses.