This project aims to develop novel, non-vaccine therapeutic strategies to prevent, control, and reduce the impact of highly pathogenic avian influenza (hpai) in poultry

The Department of Agriculture Animal and Plant Health Inspection Service awarded a $1.264 million cooperative agreement to the Regents of the University of Minnesota on February 2, 2026, under the Plant and Animal Disease, Pest Control, and Animal Care program (CFDA 10.025).

The recipient will develop non-vaccine therapeutic strategies to prevent, control, and reduce the impact of highly pathogenic avian influenza in poultry by using immune-priming compounds delivered orally or via spray application. These compounds induce innate immune memory through epigenetic alterations, enabling birds to mount faster and more effective responses upon exposure to infection. The project focuses on egg-laying chickens and turkeys, with potential applicability to other poultry species, and targets a broadly conserved innate immune mechanism that may offer cross-protection against multiple HPAI strains.

Work will proceed in three phases: screening candidate compounds in vitro using chicken macrophage cell lines and primary leukocytes to identify those inducing trained immunity; validating top-performing compounds in vivo in HPAI-challenged layer chickens to evaluate immune activation, viral clearance, and disease outcomes; and adapting the most promising treatments for commercial use through field trials in layer chicken and turkey flocks to assess feasibility, cost-effectiveness, and real-world protection. Expected outcomes include identification of effective immune-priming compounds and mechanistic insights into trained immunity.

Performance occurs in Minnesota. The period of performance runs from February 2, 2026, through February 1, 2029. The assistance type is a cooperative agreement.

We propose to enhance disease tolerance and resilience to hpai by training innate immune cells using immune-priming compounds delivered orally or via spray application. These compounds induce innate immune memory through epigenetic alterations, enabling birds to mount faster and more effective responses upon exposure to infection. This enhanced immunity is expected to increase tolerance to infection, reduce viral replication and shedding, and limit transmission. By strengthening the birds' ability to manage low-dose viral challenges, this approach may improve survival and overall flock health. The project will focus on EGG-laying chickens and turkeys, with potential relevance to other poultry species. Because IT targets a broadly conserved innate immune mechanism, the strategy may offer cross-protection against multiple hpai strains. If successful, IT will provide a scalable and practical alternative to current control methods, helping producers maintain flock resilience and reduce reliance on mass depopulation during outbreaks. The project will proceed in three phases. First, we will screen candidate compounds in vitro using chicken macrophage cell lines and primary leukocytes, identifying those that induce trained immunity based on epigenetic and immunological markers. Second, we will validate the top-performing compounds in vivo by evaluating their ability to enhance immune activation, support viral clearance, and improve disease outcomes in hpai-challenged layer chickens. Finally, we will adapt the most promising treatments for commercial use and conduct field trials in layer chicken and turkey flocks to assess feasibility, cost-effectiveness, and realworld protection. Expected outcomes include the identification of effective immune-priming compounds and mechanistic insights into trained immunity in poultry. We will generate in vivo data demonstrating improved hpai tolerance and disease resilience, develop standardized treatment protocols, and produce peer-reviewed publications. A final report will summarize safety profiles and provide recommendations for integration into poultry health programs. This work will benefit EGG producers, turkey and broiler integrators, and stakeholders across the poultry supply chain by supporting a proactive, science-based approach to sustainable flock health and disease control.