A multivalent capsule vaccine protects against Klebsiella pneumoniae bloodstream infections in healthy and immunocompromised mice

Klebsiella pneumoniae is a leading cause of nosocomial infections, bacteremia, and worldwide mortality. Further, a drastic rise in antibiotic-resistant isolates poses an urgent threat to humanity. Unfortunately, despite its clinical importance, a licensed K. pneumoniae vaccine is not yet available. Here, we report on the production and characterization of the broadest K. pneumoniae capsule bioconjugate vaccine to date. We tested this vaccine for its immunogenicity, functionality, efficacy, and antibody durability against a variety of K. pneumoniae isolates in a murine bacteremia model. We also established an immunocompromised murine model of bacteremia to better recapitulate human infection and tested our vaccine's efficacy in this background. The tetravalent capsule vaccine is highly immunogenic in mice, generating a robust immune response against all capsule types included (K1, K2, KL102, and KL107). Further, the generated antibodies persist for at least 6 months. The vaccine-induced antibodies are highly functional against a variety of clinical isolates of K. pneumoniae, including both classical and hypervirulent strains. Finally, the vaccine led to increased survival after bacteremia challenge compared to placebo-immunized mice. Our findings confirm that a capsule-based bioconjugate vaccine has clinical potential in preventing K. pneumoniae infections. These experiments signify much-needed progress towards a multivalent vaccine to combat this increasingly troublesome pathogen.