Divergent humoral immune signatures in response to Klebsiella pneumoniae bacteremia.

Abstract

OBJECTIVES: Klebsiella pneumoniae is an increasingly threatening global pathogen with high rates of antibiotic resistance and no licensed vaccines available. Despite its worldwide importance, little is known about the human adaptive immune response to K. pneumoniae infection. METHODS: Herein we observed the longitudinal antibody responses of three immunocompetent patients hospitalized with K. pneumoniae bacteremia. We analyzed the human serum for antibody titers and in vitro functionality. Further, serum function was evaluated via an in vivo mouse model. RESULTS: We found that in each case, anti-K. pneumoniae antibodies against the infecting strain were still detectable a year after the initial infection. Serum bactericidal assays revealed a wide spectrum of antibody functionality against the inciting strains in vitro. Finally, mice were passively immunized with three patients' sera; one of these sera protected mice from lethal bacteremia challenge with its matched K. pneumoniae strain. CONCLUSIONS: These results highlight variability in the human humoral immune response to K. pneumoniae bacteremia and stress the importance of studying multiple aspects of antibody-mediated protection to inform vaccine design.