SERUM ANTIBODY RESPONSES AGAINST CARBAPENEM-RESISTANT KLEBSIELLA PNEUMONIAE IN INFECTED PATIENTS

Abstract

BackgroundCapsular polysaccharide (CPS) heterogeneity within carbapenem-resistant Klebsiella pneumoniae (CR-Kp) strain ST258 must be considered when developing CPS-based vaccines. We sought to characterize CPS-specific antibody responses elicited by CR-Kp infected patients. MethodPlasma and bacterial isolates were collected from 33 hospital patients with positive CR-Kp culture. Isolates capsule were typed by wzi sequencing. Reactivity and measures of efficacy of patient antibodies were studied against 3 prevalent CR-Kp CPS types (wzi29, 154 and 50). ResultsHigh IgG titers against wzi154 and wzi50 CPS were documented in 79% of infected patients. Patient-derived (PD) IgGs agglutinated CR-Kp and limited growth better than naive IgG, and promoted phagocytosis of strains across the serotype isolated from their donors. Additionally, poly-IgG from wzi50 and wzi154 patients promoted phagocytosis of non-concordant CR-Kp serotypes. Such effects were lost when poly-IgG was depleted of CPS-specific IgG. Additionally, mice infected with wzi50, wzi154, and wzi29 CR-Kp strains pre-opsonized with wzi50 patient-derived IgG exhibited lower lung CFU than controls. Depletion of wzi50 Abs reversed this effect in wzi50 and wzi154 infections, whereas wzi154 Ab depletion reduced Poly-IgG efficacy against wzi29 CR-Kp. ConclusionsWe are first to report cross-reactive properties of CPS-specific Abs from CR-Kp patients through both in-vitro and in-vivo models. ImportanceCarbapenem-resistant Klebsiella pneumoniae is a rapidly emerging public health threat that can cause fatal infections in ~40-50% of immunocompromised patients. Due to its resistance to nearly all antimicrobials, development of alternate therapies like antibodies and vaccines are urgently needed. Capsular polysaccharides are emerging as important immunotargets as they are a crucial for Klebsiella pneumoniae pathogenesis. Studying how hosts immune system protect against specific bacteria such as Klebsiella pneumoiniae, with respect to their specific capsule-type is crucial to develop effective anti-CPS immunotherapies. In this manuscript, we are the first to characterize humoral responses developed in infected patients against carbapenem-resistant Klebsiella pneumoniae expressing different wzi-capsule types. This study is the first to report efficacy of cross-reactive properties of CPS-specific Abs in both in-vitro and in-vivo models.