Semisynthetic Glycoconjugate\nVaccine Lead against Klebsiella pneumoniae Serotype O2afg Induces Functional\nAntibodies and Reduces the Burden of Acute Pneumonia

Carbapenem-resistant Klebsiella pneumoniae (CR-<i>Kp</i>) bacteria\nare a serious global health concern\ndue to their drug-resistance to nearly all available antibiotics,\nfast spread, and high mortality rate. O2afg is a major CR-<i>Kp</i> serotype in the sequence type 258 group (KPST258) that\nis weakly immunogenic in humans. Here, we describe the creation and\nevaluation of semisynthetic O2afg glycoconjugate vaccine leads containing\none and two repeating units of the polysaccharide epitope that covers\nthe surface of the bacteria conjugated to the carrier protein CRM<sub>197</sub>. The semisynthetic glycoconjugate containing two repeating\nunits induced functional IgG antibodies in rabbits with opsonophagocytic\nkilling activity and enhanced complement activation and complement-mediated\nkilling of CR-<i>Kp</i>. Passive immunization reduced the\nburden of acute pneumonia in mice and may represent an alternative\nto antimicrobial therapy. The semisynthetic glycoconjugate vaccine\nlead against CR-<i>Kp</i> expressing O2afg antigen is awaiting\npreclinical development.