Recombinant hemagglutinin protein and DNA-RNA-combined nucleic acid vaccines harbored by yeast elicit protective immunity against H9N2 avian influenza infection

for controlling avian influenza virus infection is crucial in scale poultry production. Yeasts are considered useful vaccine vehicles for the delivery of antigens, which has been used to protect human and animal health. We report here the development of H9N2 strain hemagglutinin (HA)based recombinant protein vaccines (rH9HA) and charomyces cerevisiae for the first time. The immunogenicsIgA, and cellular immune responses. The reshape and diversification of gut microbiota and an enriched Lactobacillus, Debaryomyces were observed after oral immunization with rH9HA or rH9-DNA-RNA yeast vaccine, which might contribute to modulate the intestinal mucosal immunity and antiviral process. Oral immunized birds with either rH9HA or rH9-DNA-RNA were effectively protected from H9N2 virus challenge. Our findings suggested that yeast-derived H9N2 HA-based recombinant protein vaccines and DNA-RNA-combined nucleic acid vaccines are feasible and efficacious, opening up a new avenue for rapid and cost-effective production of avian influenza vaccines to achieve good protection effect.