The multivalent vaccine ‘dramatically reduced signs of illness and protected from death’, even when subjects were exposed to flu strains different from those used in making the vaccine, according to research in animal models which was published last week.
Researchers from Penn Medicine in the US are now designing human clinical trials for the vaccine.
Pandemic punch
Current flu vaccines are ‘seasonal’ vaccines that protect against recently circulating strains, but would not be expected to protect against new pandemic strains such as the 1918-1919 Spanish flu pandemic.
The strategy employed by Penn Medicine researchers is to vaccinate using immunogens—a type of antigen that stimulates immune responses—from all known influenza subtypes in order to elicit broad protection.
The resulting vaccine is not expected to provide ‘sterilizing’ immunity that completely prevents viral infections; rather, it 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.
The vaccine prompts production of copies of a key flu virus protein, the hemagglutinin protein, for all 20 influenza hemagglutinin subtypes—H1 through H18 for influenza A viruses, and two more for influenza B viruses (Immunizing against all these subtypes would pose a challenge for other vaccine technologies; but becomes ‘relatively easy’ with mRNA tech, according to the researchers).
In mice, the mRNA vaccine elicited high levels of antibodies, which stayed elevated for at least four months, and reacted strongly to all 20 flu subtypes. Moreover, the vaccine seemed relatively unaffected by prior influenza virus exposures, which can skew immune responses to conventional influenza vaccines. The researchers observed that the antibody response in the mice was strong and broad whether or not the animals had been exposed to flu virus before.
“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,” said study senior author Scott Hensley, PhD, a professor in of Microbiology at in the Perelman School of Medicine.
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.
Building on COVID-19 success
In using the same mRNA tech as the Pfizer and Moderna COVID-19 vaccines; the vaccine would effectively work in the same way as how first-generation COVID vaccines provided protection against subsequent strains.
“It would be comparable to first-generation SARS-CoV-2 mRNA vaccines, which were targeted to the original Wuhan strain of the coronavirus,” Hensley said. “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.”
In principle, the same multivalent mRNA strategy can be used for other viruses with pandemic potential.