Advancing Bird Flu Vaccine Development through Organoid Research

A group of researchers from the Texas Biomedical Research Institute has created an innovative, proof-of-concept vaccine to guard against a bird flu strain currently circulating in the United States. This project was headed by Professor Luis Martinez-Sobrido, Ph.D., and Staff Scientist Ahmed M. Elsayed, Ph.D., who recently published preliminary findings in npj Vaccines.

The team developed a live attenuated vaccine containing a weakened form of the avian influenza virus that has affected poultry and dairy cows across the U.S. since March 2024. The new vaccine candidate demonstrated high efficacy in cell cultures and animal models, where just a single dose was sufficient to shield mice from fatal H5N1 infection.

Currently, they are working on developing variations of this vaccine that can combat other bird flu strains prevalent in global hotspots. Highly pathogenic avian influenza is naturally carried by migratory birds but is lethal for domesticated chickens and turkeys. Their ultimate goal is to create a vaccine capable of providing protection against multiple bird flu strains or even universal vaccination.

Since H5N1 has been observed spreading to various mammal species, including sea lions, cats, and now dairy cattle, there are growing concerns over the virus potentially evolving to spread among humans, possibly leading to a more severe pandemic. Dr. Elsayed emphasized that while existing emergency stockpiles of inactivated bird flu vaccines have worked against the current H5N1 strain, live attenuated vaccines could offer longer-lasting and stronger protection.

The Texas Biomed researchers reported in Emerging Microbes & Infections that the current U.S. bird flu strain alters human airway cells, causing scar tissue formation. Dr. Martinez-Sobrido and his team identified a potential therapy target to minimize harmful inflammation linked with avian influenza infection.

The researchers utilized human airway organoids for their project, which are miniature 3D models of specific tissues mimicking the physical structure of airway lining or epithelium. These models contain four critical tracheal cell types and provide more detailed tissue response insights than single-cell lines.

"When exposed to a bird flu strain first detected in Texas dairy cattle last spring, our organoids exhibited significant inflammatory responses, including scar tissue development," said Dr. Rothan. These reactions were much more severe with H5N1 compared to seasonal swine flu strain H1N1.

The team found that briefly inhibiting the key driver of inflammation—known as the ROCK pathway—reduced scarring by focusing on the enzyme ROCK1, which proved more effective than targeting another enzyme called ROCK2. This discovery could enhance treatment for both bird flu and other respiratory viruses like SARS-CoV-2.