Oral Yeast-Cell Microcapsule-Mediated DNA Vaccines Against Clostridium perfringens Induce Effective Intestinal Immunity and Modulate Gut Microbiota

<b>Background/Objectives:</b><i>Clostridium perfringens</i> is a common opportunistic pathogen that causes gastrointestinal diseases in livestock and poultry. Our preliminary research has demonstrated that administering oral yeast-cell microcapsule (YCM)-mediated DNA vaccines can effectively stimulate mucosal immunity, thereby preventing the occurrence of gastrointestinal diseases. <b>Methods:</b> In this study, the <i>C. perfringens</i> α-toxin gene was first cloned and the H126G and C-terminal (C247-370) mutations were created. The corresponding DNA vaccine cassettes driven by a CMV promoter were constructed and were cloned into a yeast shuttle vector. Recombinant yeast strains transformed with these shuttle vectors were then prepared as the YCMs for the subsequent oral immunization of mice. <b>Results:</b> Oral administration of recombinant YCMs can induce an effective immune response, and the H126G YCM performed much better than C247-370. Further evidence suggested that YCM administration may contribute to modulating the gut environment by altering gut microbiota and enhancing bacterial richness. <b>Conclusions:</b> Our study indicated that the oral administration of YCM-mediated DNA vaccines can induce effective intestinal immunity and may also alter the composition of the gut microbiota, suggesting a promising candidate vaccine strategy against <i>C. perfringens</i>-induced animal diseases.