GMMA as delivery system for Klebsiella pneumoniae O-antigens and K-antigens

Klebsiella pneumoniae (Kp) is a major cause of healthcare-associated infections in developed countries and neonatal sepsis in low- and middle-income countries, posing a global public health threat due to its antimicrobial resistance. Although potential vaccine targets have been identified, no vaccine is currently licensed for Kp. Two classes of polysaccharides displayed on the Kp surface-capsular polysaccharides (KAg) and lipopolysaccharide O-antigens (OAg)-determine serotypes and represent promising candidates for vaccine development. We purified GMMA (Generalized Modules for Membrane Antigens), from hypervesiculating genetically engineered Kp strains which effectively display both OAg and KAg polysaccharides, and we used them to investigate OAg-mediated cross-reactivity and immuno-interference between OAg-KAg combinations. In mice, GMMA elicited strong antibody responses against both polysaccharides, with no negative impact on OAg immunogenicity in presence of KAg. These findings support the potential of combining multiple GMMA to achieve broad serotype coverage in Kp vaccines.