Universal flu vaccine candidate protects against severe infection, study finds

The quest for a universal flu vaccine has been a long and challenging journey for scientists. Each year, millions of people are vaccinated to protect against severe respiratory illnesses caused by influenza viruses. However, current vaccines vary in effectiveness, offering between 10% and 60% protection depending on the strain and season.

This inconsistency arises because the flu virus mutates rapidly, making it difficult to predict which strains will dominate each season. As a result, seasonal vaccines often fail to protect against the most virulent flu strains.

Researchers are now exploring innovative ways to create a universal flu vaccine that could provide protection against all strains of the virus, potentially lasting for multiple seasons. One such effort, recently published in the Journal of Virology, brings new hope.

Researchers at the Cleveland Clinic’s Lerner Research Institute have made significant progress toward developing a universal flu vaccine that has shown promising results in animal models. This experimental vaccine has elicited a strong immune response and protected the animals against severe infection after exposure to the flu virus.

The research team, led by Ted M. Ross, Ph.D., Director of Global Vaccine Development at Cleveland Clinic, is building on previous studies to achieve broader protection. The group is employing a cutting-edge technique called COBRA (Computationally Optimized Broadly Reactive Antigens) to design their vaccine.

COBRA analyzes thousands of genetic sequences of influenza strains across multiple seasons to identify which amino acids in the virus's proteins remain consistent. By focusing on these conserved proteins, the researchers aim to develop a vaccine that targets the most crucial parts of the virus that are less likely to change from season to season.

The team identified proteins from several flu subtypes, including H1, H3, H2, H5, and H7. These subtypes are significant because some, such as H5 (avian flu), pose a serious pandemic risk. The avian H5N1 flu has previously led to human deaths, and in March 2024, the virus was found in dairy cattle in Texas.

Since then, the virus has spread across multiple species, affecting both humans and animals. This broad coverage highlights the importance of developing vaccines that can protect against more than just the common seasonal strains.

“We’ve shown that our H5 vaccine covers many different clades,” said Naoko Uno, Ph.D., the lead researcher in this study. She explained that the COBRA methodology allowed the team to "whittle down" the list of potential proteins to include only those most effective at eliciting a sustained immune response. The vaccine created is designed like a "greatest hits" album, including only the best proteins for stimulating the immune system.

The vaccine was tested in animals by administering it intranasally, a method that has been gaining attention for flu vaccines. Unlike the traditional intramuscular flu shots, intranasal delivery targets the mucosal surfaces in the nose and respiratory tract, where flu viruses often enter.

This method not only elicits a strong systemic immune response but also stimulates local immune responses in the areas where the virus is most likely to attack. After receiving the vaccine, the animals developed antibodies against the virus, and when they were exposed to the flu pathogen, they were protected from developing a full-blown infection.

This approach has the potential to significantly reduce the spread of the virus, making it harder for it to jump from one person to another. Additionally, intranasal delivery could improve patient compliance since it’s easier to administer and less painful than a shot. As Dr. Uno explained, "This method could also be beneficial for other viral diseases, like dengue."

Current flu vaccines are made from inactivated or attenuated flu viruses, most of which are grown in embryonated chicken eggs. While effective, these vaccines have limitations, especially for the elderly or immunocompromised individuals. Recombinant protein vaccines, like the one Ross’s group is developing, may offer a better alternative.

These vaccines are not grown in eggs, meaning they avoid the egg-adapted mutations that can weaken the vaccine’s effectiveness. Furthermore, recombinant vaccines have shown better protection against flu-related hospitalizations in women, younger adults, and people without high-risk conditions.

The COBRA technology could revolutionize the way vaccines are made, not just for influenza but for other diseases as well. By generating a consensus sequence from thousands of viral isolates, researchers can create vaccines that offer broad protection against a wide range of strains.

Studies have already shown that mice vaccinated with COBRA-derived vaccines developed protective immune responses against both seasonal and pre-pandemic flu strains when given intramuscularly.

Most flu vaccines today are delivered by injection, which stimulates a systemic immune response but not as much of a local one in the respiratory tract. Intranasal delivery, on the other hand, provides robust local protection at the site where the virus enters the body.

This can significantly reduce the likelihood of infection and transmission. Vaccines delivered this way may also have practical advantages, such as reduced sanitary costs and ease of administration. For them to be effective, however, they must be formulated with adjuvants—substances that enhance the body’s immune response to the vaccine.

The Cleveland Clinic researchers are hopeful that human trials of their universal flu vaccine could begin within one to three years. Meanwhile, they continue collaborating with international teams in India and the European Union to advance the development of this promising candidate.

If successful, this vaccine could change the way we protect against influenza and help prevent future pandemics

Note: Materials provided above by The Brighter Side of News. Content may be edited for style and length.

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