Antibodies Against Klebsiella: Key for Vaccine Development?

TOPLINE:

Antibody responses to the O-specific polysaccharide of Klebsiella pneumoniae were immunogenic, with cross-reactivity among related subtypes; however, capsule interference with O-specific polysaccharide antibody binding highlighted the limits of O-specific polysaccharide–based vaccines.

METHODOLOGY:

• Researchers conducted a prospective cohort study at a tertiary hospital to compare antibody responses to the O-specific polysaccharide (a potential target for vaccine development against K pneumoniae) among patients with confirmed K pneumoniae bloodstream infection and those without it.
• They enrolled 69 patients with confirmed K pneumoniae bloodstream infection (median age, 68 years; 64% men), 36 healthy control individuals (median age, 47 years; 44% men), and 25 control individuals with Enterococcus bloodstream infection (median age, 66 years; 68% men) between July 2021 and August 2022.
• Plasma was collected during hospitalization and follow-up visits as needed for patient care, with excess plasma used for this study after routine testing.
• The primary outcome was the plasma immunoglobulin G (IgG), IgM, and IgA antibody responses to O-specific polysaccharide antigens.
• The secondary outcomes included functional measurements of the immune response, such as antibody-dependent complement deposition and antibody-dependent neutrophil phagocytosis, and plasma antibody binding.

TAKEAWAY:

• Serotypes O1, O2, O3, and O5 accounted for 83% of K pneumoniae bloodstream infections, and the most common capsular polysaccharide serotype was K2.
• The median IgG responses to O- specific polysaccharide antigens in patients with K pneumoniae bloodstream infection were 11.9 times higher for O1v1, 17.8 times higher for O1v2, 12 times higher for O3b, 29.9 times higher for O2v1, and 16.8 times higher for O5 (all P < .05) than those in healthy control individuals.
• IgG, IgM, and IgA antibody responses against O1v1 and O1v2, O2v1 and O2v2, and O3/O3a and O3b subtypes, as well as against O1 and O2 serotypes, were strongly correlated (all P < .05).
• An analysis of four patients with variable levels of capsular polysaccharide expression revealed that capsular polysaccharide presence interfered with O-specific polysaccharide antibody binding and antibody-dependent complement deposition.

IN PRACTICE:

“Our results demonstrate that O-specific polysaccharide is a dominant target of the immune response to invasive K pneumoniae and that closely related O-specific polysaccharide subtypes are cross-reactive,” the authors wrote.

SOURCE:

This study was led by Wontae Hwang, PhD, Division of Infectious Diseases, Massachusetts General Hospital, Boston. It was published online on February 11, 2025, in The Lancet Microbe. 

LIMITATIONS:

Potential bias existed due to the loss of longitudinal data on immune responses in patients who died or were lost to follow-up. The investigation did not quantify antibody responses to specific capsular polysaccharide serotypes due to their nondominance. The study focused on blood culture–positive invasive K pneumoniae infection, which may not have represented the full spectrum of the invasive disease. Additionally, the analysis of capsule production’s interference with antibody binding was limited to a small subset of patients. 

DISCLOSURES:

This study was supported by a grant from the National Institute of Allergy and Infectious Diseases. Two authors reported having financial stakes in the vaccine research company, and some authors reported holding patents for Klebsiella and Pseudomonas vaccines. 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.