Antibody responses in Klebsiella pneumoniae bloodstream infection: a prospective cohort study.

Summary

In a prospective cohort of 69 confirmed K. pneumoniae bloodstream infections, O-specific polysaccharide (O-PS) induced strong, cross-reactive Ig responses compared with controls. However, capsular polysaccharide—even in non-hyperencapsulated strains—reduced O-PS–targeted antibody binding and complement deposition, challenging the efficacy of O-PS–only vaccine designs.

Key Findings

• O-specific polysaccharide was immunogenic in K. pneumoniae bloodstream infection, with 10–30-fold higher IgG responses versus healthy controls.
• Cross-reactivity was observed between closely related O-PS subtypes (e.g., O1v1–O1v2, O2v1–O2v2, O3–O3b) and between O1 and O2.
• Capsule production inhibited O-PS–targeted antibody binding and complement deposition in both hyperencapsulated and non-hyperencapsulated isolates.

Clinical Implications

K. pneumoniae vaccine strategies should consider capsular interference; multicomponent vaccines that include capsule-targeting or protein antigens may be required rather than O-PS alone.

Limitations

• Single-center study with a moderate sample size
• Clinical protection endpoints were not assessed; immunogenicity may not translate directly to efficacy due to capsular masking

Future Directions

Design and testing of multicomponent vaccines that overcome capsular shielding; assessment of functional opsonophagocytic activity and clinical protection in diverse serotypes.