A universal flu vaccine that offers long-term protection against multiple strains of influenza remains an elusive goal. A new research suggests scientists are making significant progress. Findings published this week in the Journal of Virology indicate that a vaccine candidate developed by researchers at Cleveland Clinic’s Lerner Research Institute has successfully triggered a strong immune response and protected animal models from severe flu infection.
The study, led by Naoko Uno, Ph.D., builds on previous work from the same team, directed by Ted M. Ross, Ph.D., Director of Global Vaccine Development at Cleveland Clinic. Encouraged by the results, the researchers hope to begin human clinical trials within the next one to three years.
Addressing the Challenges of Seasonal Flu Vaccine
Annual flu vaccines provide protection against severe infection, but their efficacy varies from year to year. Because the influenza virus mutates rapidly, predicting which strains will dominate each flu season is difficult. Current vaccines contain proteins from three or four circulating influenza subtypes—such as H1N1, H3N2, and Influenza B—but they may not always match the most virulent strains.
“We want to make sure our vaccine can span multiple seasons, not just one, and protect against all the strains that affect humans,” said Uno.
To create a broader and more effective vaccine, the team employed a methodology known as COBRA (Computationally Optimized Broadly Reactive Antigens). By analyzing thousands of genetic sequences from pathogenic influenza strains over multiple seasons, they identified conserved amino acids—building blocks of proteins that remain stable across different virus variants.
Designing a Vaccine with Pandemic Preparedness in Mind
Through COBRA analysis, researchers identified key proteins from multiple influenza subtypes, including H1, H3, H2, H5, and H7. While H1 and H3 are commonly targeted by existing vaccines, H5 and H7 strains, often associated with avian influenza, pose a pandemic threat. The recent detection of H5N1 in dairy cattle in Texas and its spread to other animals. This includes sea lions, birds, and alpacas, underscores the urgency of broad-spectrum flu protection.
“We’ve been able to whittle down this list to say these are the best at spanning multiple seasons and eliciting a broadly reactive antibody response,” Uno explained. “It’s like creating a greatest hits album—we want to put only the best ones back in the vaccine.”
Promising Results and Next Steps
In their latest study, researchers administered the vaccine candidate intranasally to animal models. Blood tests four weeks later confirmed the development of virus-specific antibodies, and when the animals were exposed to the virus, they were protected against infection.
The research team is now working to advance testing efforts in the U.S., with Ross leading the domestic initiative and Uno collaborating with researchers in India and the European Union to expand global studies.
Uno also noted that the COBRA methodology may have applications beyond influenza. The approach could be used to identify optimal proteins for mRNA vaccines or other biomolecular treatments, potentially aiding the development of vaccines for viruses such as dengue.
“This can be used in a lot of viruses,” she said, signaling broader implications for infectious disease prevention.
Reference: Naoko Uno, Thomas Ebensen, Carlos A. Guzman, Ted M. Ross. Intranasal administration of octavalent next-generation influenza vaccine elicits protective immune responses against seasonal and pre-pandemic viruses. Journal of Virology, 2024.
