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Penn scientists develop 20-subtype mRNA influenza v

PHILADELPHIA — An experimental mRNA-based vaccine against all 20 known subtypes of the influenza virus provided comprehensive protection against otherwise deadly strains of influenza in early testing, and may one day serve as a general preventive measure against future influenza pandemics, according to researchers from the university’s Perelman School of Medicine of Pennsylvania.

The “multivalent” vaccine the researchers describe in a paper published today Science, uses the same messenger ribonucleic acid (mRNA) technology used in Pfizer and Moderna’s SARS-CoV-2 vaccines. This mRNA technology that made these COVID-19 vaccines possible was developed at Penn. Tests in animal models showed that the vaccine dramatically reduced signs of the disease and protected from death, even when the animals were exposed to different strains of influenza than those used to make the vaccine.

“The idea here is to have a vaccine that gives people a baseline level of immune memory for different strains of flu so that there will be far fewer illnesses and deaths in the next flu pandemic,” said the study’s senior author Scott Hensley, Ph.DProfessor of Microbiology at the Perelman School of Medicine.

Hensley and his lab collaborated with the mRNA vaccine pioneer’s lab on the study Drew Weissman, MD, PhDthe Roberts Family Professor of Vaccine Research and Director of Vaccine Research at Penn Medicine.

Influenza viruses regularly cause pandemics with enormous death tolls. The most famous of these was the “Spanish flu” pandemic of 1918-19, which killed at least ten million people worldwide. Influenza viruses can circulate in birds, pigs, and other animals, and pandemics can begin when one of these strains jumps to humans and acquires mutations that make it better suited to spread among humans. Current flu vaccines are merely “seasonal” vaccines that protect against recently circulating strains but are not expected to protect against new pandemic strains.

The strategy used by Penn Medicine researchers is to vaccinate with immunogens – a type of antigen that stimulates the immune response – 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 shows that the vaccine elicits a memory immune response that can be quickly recalled and adapted to new pandemic virus strains, significantly reducing serious illness and death from infection.

“It would be comparable to first-generation SARS-CoV-2 mRNA vaccines that targeted the original Wuhan strain of the coronavirus,” Hensley said. “Against later variants like Omicron, these original vaccines did not completely block viral infections, but they still provide durable protection against serious illness and death.”

When the experimental vaccine is injected and taken up by recipients’ cells, it begins making 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.

“For a conventional vaccine, immunization against all of these subtypes would be very challenging, but with mRNA technology it’s relatively easy,” Hensley said.

In mice, the mRNA vaccine elicited high levels of antibodies that remained elevated for at least four months and responded strongly to all 20 influenza subtypes. In addition, the vaccine appeared to be relatively unaffected by previous influenza virus exposures, which can confound the immune response to conventional influenza vaccines. The researchers observed that the antibody response in the mice was strong and broad regardless of whether the animals had been previously exposed to the flu virus or not.

Hensley and his colleagues are designing human clinical trials, he said. The researchers believe that if these studies are successful, the vaccine could be useful in inducing long-term immune memory against all influenza subtypes in people of all ages, including young children.

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

In principle, the same multivalent mRNA strategy can also be used for other viruses with pandemic potential, including corona viruses.

Research was supported by the National Institute of Allergy and Infectious Diseases (75N93021C00015, 75N93019C00050, 1R01AI108686, and R56AI150677).


Penn Medicine is one of the world’s leading academic medical centers dedicated to the related missions of medical education, biomedical research and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (established in 1765 as the country’s first medical school) and the University of Pennsylvania Health Systemwhich together form a $9.9 billion company.

According to a US News & World Report survey of research-oriented medical schools, the Perelman School of Medicine has been ranked among the top medical schools in the United States for more than 20 years. The school is consistently ranked among the nation’s top recipients of funding from the National Institutes of Health with $546 million in fiscal 2021.

University of Pennsylvania Health System patient care facilities include: the Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center – recognized by US News & World Report as one of the top honor roll hospitals in the country – Chester County Hospital; Lancaster General Health; Penn Medicine Princeton Health; and Pennsylvania Hospital, the country’s first hospital, founded in 1751. Other facilities and companies include Good Shepherd Penn Partners, Penn Medicine at Home, Lancaster Behavioral Health Hospital and Princeton House Behavioral Health.

Penn Medicine is supported by a talented and dedicated workforce of more than 52,000 associates. The organization also has alliances with leading community health care systems in southeastern Pennsylvania and southern New Jersey, creating more options for patients regardless of where they live.

Penn Medicine is committed to improving life and health through a variety of community-based programs and activities. In fiscal 2021, Penn Medicine committed more than $619 million to benefit our community.

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