An experimental mRNA vaccine against all subtypes of influenza virus

Promising results in animal models help pave the way for clinical trials.

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A new mRNA flu vaccine could one day be used as a general preventative measure against future flu pandemics, reported researchers from the Perelman School of Medicine at the University of Pennsylvania. The vaccine was effective against all 20 known subtypes of the influenza virus.

As mentioned above, this multivalent vaccine uses the same mRNA technology employed in the Pfizer and Moderna SARS-CoV-2 vaccines. Even when the animals were exposed to flu strains distinct from those employed in the vaccine’s development, tests on animal models revealed that the vaccine significantly decreased symptoms and protected against death.

Study senior author Scott Hensley, Ph.D., a professor of Microbiology at the Perelman School of Medicine, said, “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.”

Scientists here used a strategy: to vaccinate using immunogens—a type of antigen that stimulates immune responses—from all known influenza subtypes to elicit broad protection.

The vaccine is not expected to provide “sterilizing” immunity that prevents viral infections. Instead, the new study shows that the vaccine elicits a memory immune response that can be quickly recalled and adapted to new pandemic viral strains, significantly reducing severe illness and death from infections.

Study senior author Scott Hensley, Ph.D., a professor of Microbiology at the Perelman School of Medicine, said“It would be comparable to first-generation SARS-CoV-2 mRNA vaccines, which were targeted to the original Wuhan strain of the coronavirus. 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.”

The experimental vaccine, when injected and taken up by the cells of recipients, starts producing copies of a key flu virus protein, the hemagglutinin protein, for all twenty influenza hemagglutinin subtypes—H1 through H18 for influenza A viruses, and two more for influenza B viruses.

The mRNA vaccination strongly responded to all 20 flu subtypes in mice and produced high antibodies that persisted at elevated levels for at least four months. Furthermore, the vaccination appeared to be generally unaffected by previous exposures to the influenza virus, which can alter immune reactions to conventional influenza vaccines. Whether or not the mice had previously been exposed to the flu virus, the researchers saw a strong and widespread antibody response in the mice.

Hensley said, “We think this vaccine could significantly reduce the chances of ever getting a severe flu infection.”

Journal Reference:

  1. Scott Hensley, Drew Weissman, et al. A multivalent nucleoside-modified mRNA vaccine against all known influenza virus subtypes. Science. DOI: 10.1126/science.abm0271