Hemagglutinin expressed by yeast reshapes immune microenvironment and gut microbiota to trigger diverse anti-infection response in infected birds

Abstract

IntroductionThe H5N8 influenza virus is a highly pathogenic pathogen for poultry and human. Vaccination is the most effective method to control the spread of the virus right now. The traditional inactivated vaccine, though well developed and used widely, is laborious during application and more interests are stimulated in developing alternative approaches.MethodsIn this study, we developed three hemagglutinin (HA) gene-based yeast vaccine. In order to explore the protective efficacy of the vaccines, the gene expression level in the bursa of Fabricius and the structure of intestinal microflora in immunized animals were analyzed by RNA seq and 16SrRNA sequencing, and the regulatory mechanism of yeast vaccine was evaluated.ResultsAll of these vaccines elicited the humoral immunity, inhibited viral load in the chicken tissues, and provided partial protective efficacy due to the high dose of the H5N8 virus. Molecular mechanism studies suggested that, compared to the traditional inactivated vaccine, our engineered yeast vaccine reshaped the immune cell microenvironment in bursa of Fabricius to promote the defense and immune responses. Analysis of gut microbiota further suggested that oral administration of engineered ST1814G/H5HA yeast vaccine increased the diversity of gut microbiota and the increasement of Reuteri and Muciniphila might benefit the recovery from influenza virus infection. These results provide strong evidence for further clinical use of these engineered yeast vaccine in poultry.

Roles and Mechanisms of NLRP3 in Influenza Viral Infection

“…The symbiotic microbiota, which consists of trillions of microorganisms, plays a crucial role in regulating various host physiological functions, such as digestion, nutrient metabolism, and immune system development [ 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 ]. Recently, mounting evidence has suggested that the gut microbiota modulates the host’s susceptibility to viral infections and contributes to various immune protective mechanisms against influenza virus infection [ 18 , 19 , 20 , 88 , 139 , 140 , 141 , 142 , 143 , 144 , 145 ]. Neomycin-sensitive bacterial communities continuously provide signals for the transcription of Il1b and Il18 , contributing to pulmonary protective immune responses during influenza virus infection [ 18 , 139 ].…”