Oral immunization of recombinant Saccharomyces cerevisiae expressing fiber-2 of fowl adenovirus serotype 4 induces protective immunity against homologous infection

Hydropericardium-hepatitis syndrome (HHS) caused by fowl adenovirus (FAdV) serotype 4 strains is a highly contagious disease that causes significant economic loss to the global poultry industry. However, subunit vaccine against FAdV-4 infection is not yet commercially available to date. This study aims to explore the potential for oral immunization of recombinant Saccharomyces cerevisiae expressing Fiber-2 of FAdV-4 as a subunit vaccine. Here, we constructed recombinant S. cerevisiae (ST1814G/Fiber-2) expressing recombinant Fiber-2 (rFiber-2), which was displayed on the cell surface. To evaluate the immune response and protective effect of live recombinant S. cerevisiae, chickens were orally immunized with the constructed live ST1814G/Fiber-2, three times at 5-day intervals, and then challenged with FAdV-4. The results showed that oral administration of live ST1814G/Fiber-2 could stimulate the production of humoral immunity, enhance the body's antiviral activity and immune regulation ability, improve the composition of gut microbiota, provide protection against FAdV-4 challenge, reduce viral load in the liver, and alleviate the pathological damage of heart, liver, and spleen for chicken. In addition, we found the synergistic effect in combining the ST1814G/Fiber-2 yeast and inactivated vaccine to trigger stronger humoral immunity and mucosal immunity. Our results suggest that oral live ST1814G/Fiber-2 is a potentially safer auxiliary preparation strategy in controlling FAdV-4 infection.