In a new study, researchers from the Perelman School of Medicine at the University of Pennsylvania found that an experimental mRNA vaccine against all 20 known influenza virus subtypes provides extensive protection against other deadly influenza virus strains in initial tests, so it could one day become a universal measure to prevent future influenza pandemics. The paper entitled “Cortical wiring by synapse type-specific control of local protein synthesis” was published in Science on November 25, 2022.
In this paper, the authors describe the “multivalent” vaccine. Tests in animal models have shown that the vaccine greatly reduces signs of disease and protects animals from death, even if they are exposed to a different strain of influenza virus than when the vaccine was made.
“Our idea is to give people a baseline immune memory of different influenza strains so that when the next influenza pandemic occurs, there will be a significant reduction in disease and death,” said Dr. Scott Hensley, a professor of microbiology at the University of Pennsylvania Perelman School of Medicine and author of the paper. The new study was conducted by Hensley and his lab collaborated with mRNA vaccine pioneer Dr. Drew Weissman, director of vaccine research at the University of Pennsylvania Perelman School of Medicine.
Influenza viruses periodically cause pandemics, causing a huge number of deaths. The most famous of these is the “Spanish flu” pandemic of 1918-1919, which killed at least tens of millions of people worldwide. Influenza viruses can circulate in birds, pigs, and other animals, and an influenza pandemic begins when one of the flu strains jumps to humans and mutates, making it more suitable for transmission in humans. The current influenza vaccine is only a “seasonal” vaccine that can prevent recent epidemics but not new pandemic strains.
The authors’ strategy is to vaccinate with immunogens from all known influenza virus subtypes—an antigen that stimulates the immune response—to cause widespread protection. The vaccine they developed is not expected to provide sterilizing immunity that completely protects against viral infection. Instead, the new study shows that the vaccine triggers a memory immune response that can be quickly activated and adapted to new pandemic influenza strains, greatly reducing serious illness and death caused by infection.
“This will be comparable to the first generation of SARS-CoV-2 mRNA vaccines, which were developed against the original SARS-CoV-2 strain,” Hensley said, “and the SARS-CoV-2 mRNA vaccines do not completely block viral infection against later SARS-CoV-2 variants, such as Omicron, but they continue to provide lasting protection against serious illness and death.”
After being injected into the recipient and ingested by the recipient’s cells, the experimental vaccine began to produce hemagglutinin protein, a key influenza virus protein, against all 20 known influenza hemagglutinin subtypes, the H1~H18 subtype of influenza A virus, and two influenza B viruses.
“Preventing all these influenza virus subtypes through immunization will be a major challenge for traditional vaccines, but it is relatively easy to use mRNA technology,” Hensley said.
In mice, the multivalent mRNA vaccine elicited high levels of antibodies that remained for at least four months and reacted strongly to all 20 influenza virus subtypes. In addition, the vaccine appears to be relatively unaffected by previous influenza virus exposure, which may affect the immune response to traditional influenza vaccines. The authors observed that the antibody responses of mice were strong and widespread regardless of whether or not they had previously been exposed to the influenza virus.