Recombinant Saccharomyces cerevisiae EBY100/pYD1-FaeG: a candidate for an oral subunit vaccine against F4+ETEC infection

Diarrheal diseases attributable to multidrug-resistant F4+ enterotoxigenic Escherichia coli (ETEC) are escalating in severity, posing significant risks to the health and safety of both humans and animals. This study used Saccharomyces cerevisiae EBY100 to display the FaeG subunit of F4 colonizing factor as an oral vaccine against F4+ ETEC infection. Mice were orally immunized twice with 10(8) CFU of EBY100/pYD1-FaeG, followed by a challenge with F4+ ETEC EC6 on day 7 post-immunization. The results showed that the recombinant strain EBY100/pYD1-FaeG orally enhanced the growth of the small intestine villi, significantly boosted the expression of tight junction proteins ( ZO-1 , Occludin, MUC2, and Claudin) (P < 0.05), and modulated the gut microbiota composition. Additionally, immunization with EBY100/pYD1-FaeG also upregulated the levels of IL-2, IL-4, and IFN-gamma in the intestines of mice (P < 0.01), while serum IgG and fecal sIgA titer significantly increased (P < 0.05). These immune responses enhanced the capacity to fight against ETEC, leading to an increased survival rate of mice and relieved damage to tissues and organs of mice infection. In summary, the study suggested that the recombinant Saccharomyces cerevisiae EBY100/pYD1-FaeG could effectively stimulate the immune response and generate specific antibodies against F4+ ETEC, showing its potential to serve as a subunit oral vaccine candidate for preventing F4+ ETEC infection.