Prevent future influenza pandemics! Science's latest research develops mRNA influenza vaccines against all known subtypes

Researchers at the University of Pennsylvania's Perelman School of Medicine say that in initial tests, an experimental mRNA-based vaccine against all 20 known subtypes of influenza viruses offered broad protection against other deadly flu strains, so it could one day become a general preventive measure
for future influenza pandemics.

The researchers describe the "polyvalent" vaccine in a paper published today in the journal Science, which uses the same messenger RNA (mRNA) technology
as the Pfizer and Moderna SARS-CoV-2 vaccines.
This messenger RNA technology that makes COVID-19 vaccines possible was pioneered by the University of
Pennsylvania.
Tests in animal models have shown that even if animals are exposed to a different strain of influenza virus than the one used to make the vaccine, the vaccine can significantly reduce signs of illness and avoid death
.

Dr Hensley, senior author of the study, said: "The idea is to develop a vaccine that gives people a baseline level of immune memory to different flu strains, so that when the next influenza pandemic occurs, there will be much
less illness and death.
"

Hensley and his lab collaborated on the research with the lab of mRNA vaccine pioneer Drew Weissman, MD and Roberts Family Professor of Vaccine Research and Director of
Vaccine Research at the Pennsylvania Medical School.

Influenza viruses periodically cause pandemics, causing a large number of deaths
.
The most famous of these was the 1918-1919 "Spanish flu" pandemic, 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 virus strains jumps
onto humans and gains a mutation that is better adapted to circulate between humans.
Current flu vaccines are only "seasonal" vaccines that protect against recently circulating strains, not new pandemic strains
.

The strategy employed by the researchers at the University of Pennsylvania School of Medicine is to vaccinate with an immunogen (an antigen that stimulates an immune response) from all known influenza subtypes for broad protection
.
The vaccine is not expected to provide a "bactericidal" immunity
that completely protects against viral infections.
Instead, the new study shows that the vaccine triggers a memory immune response that quickly recalls and adapts to new pandemic strains, significantly reducing deaths
from severe illness and infection.

"This will be comparable to the first generation of SARS-CoV-2 mRNA vaccines, which targets the original coronavirus strain
," Hensley said.
"For later variants, such as Omicron, these initial vaccines did not completely stop viral infections, but they continued to provide long-lasting protection against severe illness and death
.
"

When the experimental vaccine is injected and taken up by the recipient's cells, it begins to produce a copy of a key influenza virus protein, the hemagglutinin protein, against all 20 influenza hemagglutinin subtypes — the H1 to H18 subtypes of influenza A and the hemagglutinin subtypes
of the other two influenza B viruses.

"Immunizing all of these subtypes will be a major challenge for 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 a strong response
to all 20 influenza subtypes.
In addition, the vaccine appears to be relatively unaffected by previous exposure to influenza viruses, which may distort the immune system's response
to traditional flu vaccines.
The researchers observed that regardless of whether the mice had been exposed to the flu virus before, their antibody response was strong and extensive
.

Hensley and his colleagues are currently designing human clinical trials, he said
.
The researchers envision that if these trials are successful, the vaccine could help inspire long-term immune memory
against all influenza subtypes in people of all age groups, including young children.

"We think this vaccine can significantly reduce the chance
of getting severe influenza," Hensley said.

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

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

Original:

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