A multi-valent Klebsiella pneumoniae capsule vaccine 2106

Abstract Description Klebsiella pneumoniae is a leading cause of nosocomial infections, neonatal sepsis, and worldwide childhood 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 created 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. Lastly, we also established an immunocompromised murine model of bacteremia infection to better recapitulate human infections, and tested our vaccine in this background. The tetra-valent capsule vaccine is highly immunogenic in mice generating a robust immune response against all capsule types included. Further the generated antibodies persisted at least 6 months in mice. 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 conjugate vaccine has clinical potential in preventing K. pneumoniae infections. This is much needed progress towards a multi-valent vaccine to combat this increasingly troublesome pathogen. Funding Sources NIH R01AI175038 NIH R41AI167078 Topic Categories Vaccines and Immunotherapy (VAC)