Progress Toward a Universal Flu Shot

For decades, the ritual has been the same: scientists predict which flu strains will dominate the coming winter, manufacturers rush to produce vaccines, and the public hopes the prediction was accurate. Often, it isn’t. However, the same mRNA technology that powered the rapid development of COVID-19 vaccines is now being adapted to solve this problem. Researchers are making significant strides toward a “universal” flu shot—a single immunization capable of protecting against all known strains of the influenza virus.

The Flaws in Current Flu Prevention

To understand the magnitude of a universal vaccine, it helps to look at why current methods fall short. Today’s flu shots are “quadrivalent,” meaning they protect against four specific strains of the virus (two Influenza A and two Influenza B).

The World Health Organization (WHO) meets twice a year to predict which strains will be most prevalent. This process happens roughly six months before the flu season begins. Unfortunately, the influenza virus mutates rapidly. By the time the vaccines are manufactured and distributed, the dominant virus in circulation may have drifted away from the strains in the shot.

This mismatch leads to variable effectiveness rates. According to the Centers for Disease Control and Prevention (CDC), vaccine effectiveness can range from 40% to 60% in a good year, but it can drop significantly lower if the prediction is off. Furthermore, most current vaccines are grown in chicken eggs. This 70-year-old method is slow and can introduce further mutations that reduce the vaccine’s potency.

The mRNA Solution: A Multivalent Approach

The breakthrough in universal flu prevention is coming from the labs that pioneered mRNA (messenger RNA) technology. Researchers at the University of Pennsylvania, including Dr. Scott Hensley and Nobel Prize winner Dr. Drew Weissman, have developed an experimental vaccine that breaks the mold of prediction-based medicine.

Instead of guessing which three or four strains will hit, this new experimental vaccine takes a “kitchen sink” approach. The team created a lipid nanoparticle vaccine that contains mRNA encoding for antigens from all 20 known subtypes of influenza A and B viruses.

How It Works

Current vaccines present the immune system with a dead or inactivated virus. mRNA vaccines work differently. They deliver a snippet of genetic code to your cells. Your cells read this code and produce a harmless piece of the virus known as the hemagglutinin protein. This trains the immune system to recognize and attack the virus if it encounters the real thing later.

The University of Pennsylvania study, published in the journal Science, demonstrated that their multivalent vaccine produced high levels of antibodies against all 20 encoded subtypes in animal trials (specifically mice and ferrets). Importantly, these antibodies remained stable for months.

Moving Beyond the "Stalk" Theory

For years, the pursuit of a universal flu shot focused on the anatomy of the virus. The influenza virus surface protein looks like a mushroom.

The Head: This part mutates constantly to evade the immune system. Current vaccines target the head.
The Stalk: This part remains consistent (conserved) across different strains.

Many scientists believed the key to a universal vaccine was targeting the stalk. While this remains a valid strategy being pursued by the National Institutes of Health (NIH), the new mRNA approach proves you do not necessarily need to find a conserved region. Because mRNA technology allows for the rapid combination of multiple genetic codes, scientists can simply include instructions for every known variation of the viral head.

This means that even if the virus drifts or shifts, the immune system has likely already seen a version of the protein that is close enough to provide protection.

Clinical Trials and Commercial Development

While the 20-subtype vaccine is currently in preclinical stages, major pharmaceutical companies are already testing mRNA flu vaccines in humans.

Moderna (mRNA-1010): Moderna has aggressively pursued an mRNA flu vaccine. Their candidate, mRNA-1010, targets the standard four seasonal strains. While early trials showed strong immune responses, the company is refining the formula to reduce side effects and improve durability. More importantly, Moderna aims to combine flu, COVID-19, and RSV protection into a single respiratory vaccine in the future.

Pfizer and BioNTech: Following their success with the COVID-19 vaccine, Pfizer and BioNTech initiated Phase 3 clinical trials for their mRNA-based influenza vaccine. Their goal is to improve upon the efficacy of traditional vaccines and utilize the speed of mRNA manufacturing to match circulating strains more closely near the start of the flu season.

GSK and CureVac: These partners are also in the race, developing modified mRNA candidates that target multiple respiratory viruses simultaneously.

The Future of Pandemic Preparedness

The implications of this research extend beyond the seasonal sniffles. Influenza pandemics occur when a new strain jumps from animals (like birds or pigs) to humans. Because humans have no prior immunity to these novel strains, the results can be devastating.

The 1918 Spanish Flu and the 2009 H1N1 “Swine Flu” were examples of such jumps. A universal vaccine containing antigens for all 20 subtypes would theoretically provide a baseline of protection against these pandemic-potential strains. If a bird flu strain (like H5N1) were to mutate and spread among humans, a population vaccinated with a universal mRNA shot would likely have a significant survival advantage.

Frequently Asked Questions

How is a universal flu shot different from the current one? The current flu shot protects against only 3 or 4 strains selected months in advance. A universal flu shot is designed to protect against a much wider range of strains (potentially all 20 subtypes), reducing the need for annual predictions.

When will a universal flu vaccine be available to the public? While mRNA seasonal flu shots are currently in advanced clinical trials (Phase 3), a true “universal” vaccine covering all strains is likely several years away. It must pass through rigorous Phase 1, 2, and 3 human trials to ensure safety and efficacy.

Will I still need a shot every year? The goal of a universal vaccine is to provide long-lasting immunity. While it might not be a “one and done” shot like measles, it could potentially replace the annual shot with a booster required only every few years.

Is mRNA technology safe for flu vaccines? mRNA technology has been administered to billions of people worldwide via COVID-19 vaccines. The safety profile is well-understood. The technology allows the body to break down the mRNA instructions shortly after use, leaving no permanent changes to your DNA.