Klebsiella pneumoniae is a frequent pathogen in antibiotic resistant nosocomial infections and a leading cause of serious bacterial neonatal infections in developing countries. , K. pneumoniae is the second most common cause of Gram-negative bloodstream infections, mainly in immunocompromised patients. Vaccines are important tools against antimicrobial resistance and nosocomial infections. Capsular polysaccharides and lipopolysaccharides are key vaccine targets. K. pneumoniae produces a diverse array of capsular polysaccharides or K antigens (78 types) compared to only 9 different lipopolysaccharides (O-antigen). A 24-valent K. pneumoniae capsular polysaccharide vaccine showed safety and immunogenicity in human trials (phase 1), however the protection coverage was not over 70%. Herein, we focus on the development of a semi-synthetic conjugate vaccine against the hypervirulent ST258 strain, which is present in 70% of the infections caused by carbapenem-resistant K. pneumoniae. The predominant LPS O-antigen expressed by the ST258 strain is galactan III (→3)-β-D-Galf-(1→3)-[α-D-Galp-(1→4)]-α-D-Galp-(1→). A series of oligosaccharides containing different lengths of galactan III were synthesized, conjugated to the carrier protein CRM197 and the immunogenicity tested in mice. The vaccine was shown to be immunogenic and cross-reactive against the LPS O-antigen.
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