Fighting bird flu: research aims to protect U.S. poultry

Bird flu, caused by highly pathogenic avian influenza (HPAI) H5N1 has become one of the most significant animal health challenges facing U.S. agriculture. Since the current outbreak began in 2022, the virus has devastated commercial and backyard poultry flocks across the country, resulting in the loss of more than 168 million birds. The outbreaks have disrupted food supplies, contributed to egg shortages, and increased costs for consumers.

...the virus has devastated commercial and backyard poultry flocks across the country, resulting in the loss of more than 168 million birds.

The impact of H5N1 extends well beyond poultry. In 2024, the virus was detected in U.S. dairy cattle for the first time, demonstrating its ability to cross species barriers and causing significant economic losses associated with reduced milk production, increased testing and biosecurity costs, and movement restrictions. Federal agencies continue to monitor infections in poultry, wild birds, dairy cattle, cats, and other mammals.  

HPAI H5N1 is widespread among wild migratory birds, which help maintain and spread the virus across North America, making eradication unlikely. Although sporadic human infections have occurred, primarily among individuals with direct exposure to infected animals, the Centers for Disease Control and Prevention (CDC) reports that the risk to the general public remains low, and there is currently no evidence of person-to-person transmission.  

The need for better vaccines

The poultry industry plays a critical role in the U.S. food supply and economy, providing affordable sources of protein and supporting thousands of jobs. Bird flu spreads easily among poultry and such outbreaks can rapidly eliminate entire flocks, creating significant animal welfare, economic, and food security concerns with serious economic consequences for farmers and disruption of food supply nationwide. Yet current strategies for controlling HPAI rely heavily on biosecurity measures, surveillance programs, and rapid outbreak responses, which often require depopulation of infected flocks to prevent further spread of the disease.  

Many experts believe that that safe and effective vaccines may be necessary as an important tool in a long-term strategy for HPAI control and protecting America’s poultry. While several avian influenza vaccines have received conditional licenses from the U.S. Department of Agriculture (USDA), significant challenges remain that preclude their widespread implementation as a prevention strategy, and no HPAI vaccine has been authorized for use at this time, except on a case-by-case basis in certain endangered or zoo species. Existing vaccine approaches may not provide the level of protection needed for broad commercial adoption and can complicate efforts to distinguish vaccinated birds from naturally infected birds, an important principle known as DIVA (Differentiating Infected from Vaccinated Animals). In addition, no HPAI vaccine is currently authorized for widespread use in U.S. poultry production.  

A USDA-Funded Research Initiative at LSU Vet Med

To help address these challenges, a multidisciplinary research team led by Dr. Mariano Carossino, associate professor of veterinary pathology at the LSU School of Veterinary Medicine, was awarded nearly $2 million through the USDA Animal and Plant Health Inspection Service (APHIS) Highly Pathogenic Avian Influenza Poultry Innovation Grand Challenge program. The team brings together expertise in vaccinology, virology, immunology, and pathology to develop innovative vaccine approaches for protecting poultry against HPAI H5N1. 

The project, titled “Nanobody-directed, M-cell-targeted mucosal vaccine against HPAI H5N1 clade 2.3.4.4b in poultry,” seeks to develop an innovative mucosal vaccine capable of providing earlier, stronger, and more practical protection for commercial poultry operations.  

Unlike conventional vaccines, the LSU-developed approach uses nanobodies, small antibody-derived molecules, to direct vaccine components specifically to specialized immune cells in the intestinal tract. 

A different approach to protection

Unlike conventional vaccines, the LSU-developed approach uses nanobodies, small antibody-derived molecules, to direct vaccine components specifically to specialized immune cells in the intestinal tract. By targeting these cells, the vaccine is designed to stimulate strong mucosal immunity at the sites where infection often begins. Creating protective immunity at these entry points may help stop the virus before infection, while also generating a broader systemic immune response. 

The research team is also incorporating advanced vaccine platforms, including self-amplifying RNA technology and replication-deficient viral vectors. These platforms are being designed for mass administration either in ovo (before chicks hatch) or through drinking water, making them practical options for large-scale poultry production systems.  

Potential impact

If successful, this research could deliver important new tools for controlling one of the most economically damaging animal diseases in recent history. The vaccine strategy is intended to:

• Provide earlier and stronger protection against HPAI H5N1.
• Support efficient vaccination of large poultry populations.
• Facilitate disease-monitoring programs through DIVA-compatible approaches that help distinguish vaccinated birds from naturally infected birds.
• Reduce losses for poultry producers and help stabilize food supplies.  

As HPAI H5N1 continues to threaten poultry and other animal species across the United States, innovative research efforts such as this USDA-supported project are helping advance the next generation of tools needed to protect animal health and strengthen America’s agriculture.