Evaluation of capsule polysaccharide (CPS)-specific antibodies for broad recognition of prominent multidrug-resistant Klebsiella pneumoniae

Klebsiella pneumoniae is primarily an opportunistic pathogen known for causing healthcare-associated infections in individuals with significant risk factors and comorbidities. These bacteria are typically multidrug-resistant (MDR), a phenotype conferred in part by the production of extended-spectrum beta-lactamases and/or carbapenemases. By comparison, so-called hypervirulent K. pneumoniae (hvKp) are defined by their ability to cause severe community-acquired infections in otherwise healthy individuals. Although hvKp lineages have historically not been MDR, there has been a recent emergence of strains with both hypervirulence and multidrug resistance phenotypes. Treatment of infections caused by MDR K. pneumoniae can be difficult, and new preventative measures are needed. As a step toward the development of a vaccine directed to prevent or moderate infections caused by these pathogens, we tested the ability of capsule polysaccharide (CPS) derived from eight selected K. pneumoniae capsule types (KLs) to elicit rabbit antibodies that recognize important KLs isolated from human infections. Seventy-one out of 84 (84.5%) contemporary K. pneumoniae clinical isolates tested were recognized by CPS-specific rabbit antisera. There was the unexpected binding of the antibodies to some isolates with KLs not included in the CPS-antigen cocktails. Notably, rabbit IgG purified from CPS-specific antisera promoted and/or enhanced human PMN bactericidal activity toward all but one of the selected clinical isolates that were not killed by PMNs outright (in the absence of specific antibody). These data provide support to the idea that a CPS-antigen cocktail could be developed to protect against the K. pneumoniae KLs that are the most frequent cause of human infections. IMPORTANCE Klebsiella pneumoniae is among the leading causes of death by infectious agents. Many of the prominent K. pneumoniae lineages are resistant to multiple classes of antibiotics, and options for treatment are limited. New countermeasures that prevent infections are needed. Here we tested the ability of capsule polysaccharide (CPS) antigen mixtures (or cocktails) to elicit rabbit antibodies that recognize K. pneumoniae from a large collection of extended-spectrum beta-lactamase-producing clinical isolates. Importantly, these antibodies had the ability to promote opsonophagocytic killing by human PMNs. Our results provide proof-of-concept for a CPS vaccine cocktail approach that could be developed to prevent infections caused by the most important K. pneumoniae lineages.