Promising bird flu vaccine advances; organoids reveal how H5N1 scars airways

Bird flu vaccine candidate highly effective in early studies

Researchers at Texas Biomedical Research Institute have developed a new, proof-of-concept vaccine to protect people from the bird flu strain currently circulating in the United States. The team, led by Professor Luis Martinez-Sobrido, Ph.D. and Staff Scientist Ahmed M. Elsayed, Ph.D., recently published initial results in npj Vaccines.

The live attenuated vaccine contains a weakened, or attenuated, version of the avian influenza virus that has sickened poultry and dairy cows throughout the U.S. since March 2024. The vaccine candidate showed high efficacy in cells and animal models. A single dose was enough to protect mice from highly pathogenic H5N1, which would otherwise be lethal.

The team is now working to develop versions of the vaccine that would address other bird flu strains circulating in hot spots around the world. Highly pathogenic avian influenza is naturally carried by migratory birds and waterfowl, but is deadly in domesticated chickens and turkeys.

“The ultimate aim is to develop a vaccine that could protect against multiple strains of bird flu, or even offer universal protection,” Dr. Elsayed said.

H5N1 has spread to a wide range of mammal species, from sea lions to cats and now dairy cattle. The current outbreak has sickened more than 70 people in the U.S. and killed at least one person to date, primarily through contact with infected livestock. Many experts are concerned the virus could evolve to spread between people, causing a more severe pandemic. The U.S. has emergency stockpiles of bird flu vaccines available, which are based on inactivated, or killed, versions of older bird flu viruses.

“Those vaccines have shown to work against the current strain of H5N1,” Dr. Martinez-Sobrido said. “However, live attenuated vaccines can offer longer-lasting and more robust protection.”

This research was funded through a pilot grant provided to Dr. Elsayed by the Texas Biomedical Forum, a philanthropic women’s organization dedicated to supporting Texas Biomed.

Organoids show how bird flu affects airway cells, reveal potential treatment target

The current strain of H5N1 bird flu circulating in the U.S. remodels the cells lining the human airway, causing scar tissue to form, researchers at Texas Biomed report in Emerging Microbes & Infections. Dr. Martinez-Sobrido and his team, led by Staff Scientist Hussin Rothan, Ph.D., identified a potential treatment target to reduce harmful inflammation associated with influenza infection.

The researchers used human airway organoids for this project. Organoids are miniature 3D models of specific tissues and have been developed in labs around the world for decades. These human airway organoids contain four critical cell types found in the trachea and they mimic the physical structure of the airway lining, or epithelium.

“They create mucus and you can see the cilia moving under the microscope,” said Dr. Rothan. “We can get much more detailed insight into tissue responses from these organoids than we can from single cell lines.”

When exposed to a version of the bird flu first detected in Texas dairy cattle last spring, the organoids showed significant inflammatory responses, including increased production of cytokine proteins, and the development of fibrotic, or scar, tissue. The inflammatory response was far more severe for H5N1 compared to infection with a seasonal swine flu strain, H1N1.

The team found that briefly inhibiting a key driver of inflammation, known as the ROCK pathway, helped reduce the scarring. Specifically, they found that inhibiting the enzyme ROCK1 was more effective than inhibiting another enzyme, ROCK2.

“This was surprising because people usually focus on ROCK2,” Dr. Rothan said. “We now need to drill down and find out more about these interactions so we can find the most effective way to limit inflammation, not only for bird flu, but other respiratory viruses that affect the airway and lungs like SARS-CoV-2.”

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About Texas Biomed

Texas Biomed is a nonprofit research institute dedicated to protecting the global community from infectious diseases. Through basic research, preclinical testing and innovative partnerships, we accelerate diagnostics, therapies and vaccines for the world’s deadliest pathogens. Our San Antonio campus hosts high containment laboratories and the Southwest National Primate Research Center. Our scientists collaborate with industry and researchers globally, and have helped deliver the first COVID-19 vaccine, the first Ebola treatment and first Hepatitis C therapy.

Papers:

Mostafa, A., Ye, C., Barre, R.S. et al. A live attenuated NS1-deficient vaccine candidate for cattle-origin influenza A (H5N1) clade 2.3.4.4.b viruses. npj Vaccines 10, 151 (2025). https://doi.org/10.1038/s41541-025-01207-9

Rothan, Hussin, Ahmed Mostafa, Mahmoud Bayoumi, Chengjin Ye, Ramya S. Barre, Anna Allué-Guardia, Aitor Nogales, Jordi B. Torrelles, and Luis Martinez-Sobrido. 2025. “Emerging Highly Pathogenic H5N1 Influenza Triggers Fibrotic Remodeling in Human Airway Organoids.” Emerging Microbes & Infections 14 (1). doi:10.1080/22221751.2025.2532684.