A Bioconjugate Vaccine Against Extra-Intestinal Pathogenic Escherichia coli (ExPEC)

<b>Background</b>: Extra-intestinal pathogenic <i>Escherichia coli</i> (ExPEC) represents a major global public health challenge due to its ability to cause diverse clinical infections, including urinary tract infections, bacteremia, neonatal meningitis, and sepsis. The growing prevalence of multidrug-resistant (MDR) ExPEC strains, which rapidly erode antibiotic efficacy, underscores vaccine development as a critical priority. Bioconjugate vaccines have emerged as a promising approach to mitigate ExPEC-associated infections. <b>Methods and Results</b>: In this study, we utilized protein glycan coupling technology (PGCT) based on oligosaccharyltransferase (OST) PglL to engineer a tetravalent bioconjugate vaccine targeting four predominant ExPEC serotypes (O1, O2, O6, and O25). We conducted a series of experiments to demonstrate the efficacy of the conjugate vaccine in eliciting humoral immune responses and inducing the production of specific antibodies against <i>Escherichia coli</i> O1, O2, O6, or O25 serotypes. <b>Conclusions</b>: This work establishes the first application of the <i>O</i>-linked PGCT system for engineering bioconjugate vaccines against ExPEC infections.