Home » Prevent future influenza pandemics! Science’s latest research develops mRNA influenza vaccine against all known subtypes — ScienceDaily

Prevent future influenza pandemics! Science’s latest research develops mRNA influenza vaccine against all known subtypes — ScienceDaily

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Prevent future influenza pandemics! Science’s latest research develops mRNA influenza vaccine against all known subtypes

Time: November 26, 2022

Source: Science

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An experimental mRNA-based vaccine targeting all 20 known subtypes of influenza virus provided broad protection against other deadly influenza strains in initial tests, according to researchers at the Perelman School of Medicine at the University of Pennsylvania. So it may one day become a general measure to prevent future influenza pandemics.

An experimental mRNA-based vaccine targeting all 20 known subtypes of influenza virus provided broad protection against other deadly influenza strains in initial tests, according to researchers at the Perelman School of Medicine at the University of Pennsylvania. So it could one day become a general preventive measure for future influenza pandemics.

The “multivalent” vaccine, which the researchers describe in a paper published today in the journal Science, uses the same messenger ribonucleic acid (mRNA) technology as the Pfizer and Moderna SARS-CoV-2 vaccines. The messenger RNA technology that makes a COVID-19 vaccine possible was pioneered at Penn. Tests in animal models have shown that the vaccine significantly reduces signs of illness and avoids death, even when the animals are exposed to a different strain of flu than the one used to make the vaccine.

Dr Hensley, the study’s senior author, said: “The idea is to develop a vaccine that would allow people to have a baseline level of immune memory against different strains of influenza so that when the next influenza pandemic strikes, there will be much less disease and death. .”

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

Influenza viruses periodically cause pandemics, causing large numbers of deaths. The most famous of these 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 epidemics occur when one of the strains jumps to humans and acquires mutations that are better suited to spreading between humans. The current flu vaccine is only “seasonal” and protects against recently circulating strains, not new pandemic strains.

The strategy employed by the Penn Medicine researchers is to vaccinate with an immunogen (an antigen that stimulates an immune response) from all known influenza subtypes to achieve broad protection. The vaccine is not expected to provide “bactericidal” immunity that completely protects against viral infection. Instead, the new study shows that the vaccine elicited a memory immune response that could quickly recall and adapt to new pandemic strains, significantly reducing deaths from severe disease and infection.

“This would be comparable to the first-generation SARS-CoV-2 mRNA vaccines, which targeted the original coronavirus strain,” Hensley said. “For later variants, such as Omicron, these initial vaccines did not completely block viral infection.” , but they continue to provide long-lasting protection against severe disease and death.”

When the experimental vaccine is injected and taken up by the recipient’s cells, it begins to produce copies of a key flu virus protein, the hemagglutinin protein, which targets all 20 influenza hemagglutinin subtypes — H1 through H1 for influenza A viruses. H18 subtype, and two other hemagglutinin subtypes of influenza B viruses.

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“Making immunity to all of these subtypes would be a major challenge with traditional vaccines, but with mRNA technology, it’s relatively easy,” Hensley said.

In mice, the mRNA vaccine elicited high levels of antibodies that persisted for at least 4 months and produced strong responses to all 20 influenza subtypes. In addition, the vaccine appears to be relatively unaffected by previous exposure to flu viruses, which may distort the immune system’s response to traditional flu shots. The researchers observed that the antibody responses in the mice were strong and widespread, regardless of whether they had been exposed to the flu virus before.

Hensley and his colleagues are currently designing human clinical trials, he said. The researchers envision that if these trials are successful, the vaccine might help spark 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 chance of getting a severe flu infection,” Hensley said.

In principle, the same multivalent mRNA strategy could be used for other viruses with pandemic potential, including coronaviruses, he added.

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

Original title:

A multivalent nucleoside-modified mRNA vaccine against all known influenza virus subtypes

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