Background: The ongoing spread of avian influenza (AI) in poultry has led to severe losses. In the United States, H5N1 outbreaks by early 2025 necessitated the culling of roughly 148 million laying hens, causing egg shortages and price spikesu200b. Although AI vaccines exist, their use in U.S. poultry has been minimal due to practical and economic barriers, including trade restrictions and vaccination. Objective: This study introduces a novel oral AI vaccine strategy using genetically engineered Saccharomyces cerevisiae (baker’s yeast) to deliver conserved antigenic fragments of the H5N1 hemagglutinin (HA) and neuraminidase (NA) proteins, together with a Salmonella-derived Pertussis-like toxin B subunit (PltB) as a mucosal. The goal is to stimulate protective mucosal immunity via feed-based administration, providing a cost-effective and scalable alternative to injectable vaccines. Methods: Conserved epitopes — specifically the HA2 subunit fusion peptide region (amino acids 1—78 of H5) and a portion of the NA1 head domain (amino acids 220—290) — were identified based on high cross-strain conservation and immunogenic. Genes encoding these segments were fused in-frame with the Salmonella PltB gene, separated by flexible linkers, under control of a yeast expression system. The recombinant yeast was grown, inactivated, and formulated into a dry powder to mix with poultry feed. Protein expression and folding were confirmed by Western blot and structural modeling.