Development of a Promising Bivalent Vaccine Against Klebsiella pneumoniae Based on Glycoengineered GMMA (geGMMA)

ABSTRACT Multidrug‐resistant Klebsiella pneumoniae constitutes a significant threat as a nosocomial pathogen, and no licensed vaccines are currently available. Generalized modules for membrane antigens (GMMA) have recently been recognized as a promising platform for developing outer membrane vesicle (OMV) vaccines against numerous infectious diseases. The study was carried out in use of the W3110 ΔwbbH‐L ΔlpxM::lpxE in which E. coli was treated in order to eliminate the endogenous polysaccharide and use two new ones (polysaccharides from Klebsiella ). The exogenous polysaccharides were accurately displayed on the surface of spontaneously released OMVs. The immune responses evoked by subcutaneous administration of these vaccines were evaluated, and the protective effects were assessed using a mouse intraperitoneal challenge model. Interference in the biosynthesis of endogenous polysaccharides (such as deleting related gene clusters) is a viable approach to increasing the yield of glycoengineered GMMA vaccines (geGMMA). The geGMMA platform, which is conducive to safer large‐scale production, lays the foundations for the development of GMMA vaccines decorated with exogenous glycan antigens derived from pathogenic bacteria.