Serum Antibody Responses against Carbapenem-Resistant Klebsiella pneumoniae in Infected Patients.

Capsular polysaccharide (CPS) heterogeneity within carbapenem-resistant (CR-) strain sequence type 258 (ST258) must be considered when developing CPS-based vaccines. Here, we sought to characterize CPS-specific antibody responses elicited by CR--infected patients. Plasma and bacterial isolates were collected from 33 hospital patients with positive CR- cultures. Isolate capsules were typed by sequencing. Reactivity and measures of efficacy of patient antibodies were studied against 3 prevalent CR- CPS types (, , and ). High IgG titers against and CPS were documented in 79% of infected patients. Patient-derived (PD) IgGs agglutinated CR- and limited growth better than naive IgG and promoted phagocytosis of strains across the serotype isolated from their donors. Additionally, poly-IgG from and patients promoted phagocytosis of nonconcordant CR- serotypes. Such effects were lost when poly-IgG was depleted of CPS-specific IgG. Additionally, mice infected with , , and CR- strains preopsonized with patient-derived IgG exhibited lower lung CFU than controls. Depletion of antibodies (Abs) reversed this effect in and infections, whereas Ab depletion reduced poly-IgG efficacy against CR- We are the first to report cross-reactive properties of CPS-specific Abs from CR- patients through both and models. Carbapenem-resistant is a rapidly emerging public health threat that can cause fatal infections in up to 50% of affected patients. Due to its resistance to nearly all antimicrobials, development of alternate therapies like antibodies and vaccines is urgently needed. Capsular polysaccharides constitute important targets, as they are crucial for pathogenesis. Capsular polysaccharides are very diverse and, therefore, studying the host's capsule-type specific antibodies is crucial to develop effective anti-CPS immunotherapies. In this study, we are the first to characterize humoral responses in infected patients against carbapenem-resistant expressing different capsule types. This study is the first to report the efficacy of cross-reactive properties of CPS-specific Abs in both and models.