According to researchers from the Perelman School of Medicine at the University of Pennsylvania, an experimental mRNA-based vaccine against all 20 known subtypes of the influenza virus provided extensive protection from otherwise lethal strains to initial test and therefore may one day serve as a universal preventative measure against a future influenza pandemic.
Penn Medicine researchers indicated that the “multivalent” vaccine, which the researchers describe in a paper published recently in the journal Science, utilizes the same mRNA technology employed in the Pfizer and Moderna SARS-CoV-2 vaccines. The mRNA technology that enabled those COVID-19 vaccines was pioneered at Penn Medicine. Animal test models revealed that the vaccine significantly diminished signs of illness and protection from death, even when the animals were exposed to influenza strains different from those used in making the vaccine.
Study senior author Scott Hensley, PhD, a professor of microbiology at the Perelman School of Medicine in Philadelphia, stated, “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.”
Dr. Hensley and his laboratory collaborated in the study with the laboratory of mRNA vaccine pioneer Drew Weissman, MD, PhD, the Roberts Family Professor in Vaccine Research and Director of Vaccine Research at Penn Medicine.
The strategy utilized by the Penn Medicine researchers is 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 completely prevents viral infections. Instead, the new study reveals that the vaccine elicits a memory immune response that can be swiftly recalled and adjusted to new pandemic viral strains, considerably diminishing severe illness and death from infections.
“It would be comparable to first-generation SARS-CoV-2 mRNA vaccines, which were targeted to the original Wuhan strain of the coronavirus,” Dr. Hensley stated. “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 researchers indicated that the experimental vaccine, when injected and taken up by the cells of recipients, starts manufacturing 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.
Dr. Hensley stated, “For a conventional vaccine, immunizing against all these subtypes would be a major challenge, but with mRNA technology it’s relatively easy.”
In mice, the mRNA vaccine provoked high levels of antibodies, which remained elevated for at least 4 months, and reacted strongly to all 20 flu subtypes. Moreover, the vaccine appeared relatively unaffected by prior influenza virus exposures, which can distort immune responses to conventional influenza vaccines. The researchers observed that the antibody response in the mice was robust and extensive whether or not the animals had been exposed to flu virus before.
Currently, Dr. Hensley and his colleagues are planning human clinical trials, and the team indicates that if those trials are successful, the vaccine may be beneficial for eliciting long-term immune memory against all influenza subtypes in individuals of all age groups, including young children.
“We think this vaccine could significantly reduce the chances of ever getting a severe flu infection,” Dr. Hensley noted.
He also indicated that in principle, the same multivalent mRNA strategy can be applied for other viruses with pandemic potential, including coronaviruses.
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