A Multivalent mRNA Vaccine That Can Protect Against 20 Flu Viruses Developed at the University of Pennsylvania

For decades, scientists have been trying to develop a universal flu vaccine. The University of Pennsylvania is now proposing a formula that contains 20 different flu antigens, which would make it effective against all known flu viruses.

Flu Shot

Scott Hensley’s lab at the University of Pennsylvania has developed a flu vaccine that can protect against 20 different strains of flu – all known strains to date. Could we one day be protected against both seasonal and pandemic flu with a single shot?

A vaccine that simultaneously protects against 20 different strains of influenza

In autumn and winter, flu viruses cause a seasonal epidemic that can be fatal for the most vulnerable. To limit the circulation of the virus and the number of deaths, a new vaccine specific to circulating strains is developed each year. Scientists have long been trying to propose a universal flu vaccine, i.e. a vaccine that immunizes against all strains of the virus, or at least the main strains in humans. Several approaches have been proposed such as a multivalent vaccine targeting the most common strains of influenza A and B, or a vaccine composed of viral antigens common to all influenza viruses and not subject to mutation.

Scott Hensley and his team chose the first approach: a multivalent vaccine, but no researcher had yet tested a formulation with 20 different viral antigens. The antigen chosen was hemagglutinin, a surface protein of influenza viruses that is different for each strain. They selected 18 hemagglutinins from influenza A viruses and two from influenza B viruses.

But that’s not all, the formula includes not only human viruses but also viruses that circulate only in animals. The mRNAs containing the genetic information for synthesizing these proteins are encapsulated in tiny lipid droplets, the same principle as Pfizer and Modena’s Covid-19 vaccines. Immunization against 20 antigens in a single injection would not be possible without mRNA technology.

Protection against future influenza pandemics

This prototype universal flu vaccine was injected into mice and ferrets, two model animals often used to study influenza. The vaccinated animals developed a strong and specific immune response to the 20 virus strains contained in the vaccine. But that’s not all, the researchers also showed that the animals were protected from serious illness and death caused by virus strains not present in the priming cocktail. This suggests that this universal vaccine could also protect against strains of pandemic influenza that have not yet infected humans.

“The idea is to have a vaccine that gives people a baseline level of immunity against several strains of flu so that there will be fewer sick and dead when the next flu pandemic occurs. We also believe that this vaccine could significantly reduce the risk of developing severe influenza,” explains Scott Hensley.

According to the pre-clinical data presented in the journal Science, the vaccine is just as effective in animals that have never had influenza as in those that have already been exposed to the virus. Translated to humans, this suggests that the same vaccine can be given to children, who are often “flu-prone”, as well as to adults. But before this vaccine can reach pharmacies, it must pass human clinical trials. The pre-clinical results presented here are strong enough to continue research in this direction.