Evaluation of vaccine-induced anti-lipopolysaccharide antibodies against clinically relevant Klebsiella pneumoniae strains to inform vaccine design
Abstract
Klebsiella pneumoniae is a leading cause of neonatal sepsis in low- and middle-income countries and is increasingly multi-drug resistant, highlighting the need for vaccines. Putative vaccine targets include the lipopolysaccharide (O antigen) and capsular polysaccharide (K antigen), but capsule may mask O antigen and limit antibody-mediated opsonophagocytosis. We evaluated the activity of O antigen-specific antibodies induced by a tetravalent bioconjugate vaccine against 146 clinical isolates representing 17 prevalent capsule types associated with neonatal sepsis. Susceptibility to antibody-mediated killing varied by capsule type: four were consistently susceptible, six showed heterogeneous responses, and seven were resistant despite remaining susceptible to K antigen-specific antibodies. Killing of susceptible strains was predominantly mediated by anti-O1 antibodies, as demonstrated by competitive inhibition with purified polysaccharides. Collectively, these findings support an antigen-sparing vaccine design strategy, in which susceptible capsule types may be replaced by a single O type, reducing vaccine complexity while maintaining broad functional coverage.
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BibTeX
@article{lawrence2026evaluation,
title = {{Evaluation of vaccine-induced anti-lipopolysaccharide antibodies against clinically relevant Klebsiella pneumoniae strains to inform vaccine design}},
author = {Robert Lawrence and Nathalie Karaky and Emma Bownes and Edward Hildebrand and Cristina Alaimo and Domenico Maione and Francesca Micoli and Kathryn E. Holt and Kelly L. Wyres and David Goldblatt},
journal = {Nature Communications},
year = {2026},
month = oct,
doi = {10.1038/s41467-026-79159-4},
url = {https://www.nature.com/articles/s41467-026-79159-4},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Evaluation of vaccine-induced anti-lipopolysaccharide antibodies against clinically relevant Klebsiella pneumoniae strains to inform vaccine design
AU - Robert Lawrence
AU - Nathalie Karaky
AU - Emma Bownes
AU - Edward Hildebrand
AU - Cristina Alaimo
AU - Domenico Maione
AU - Francesca Micoli
AU - Kathryn E. Holt
AU - Kelly L. Wyres
AU - David Goldblatt
PY - 2026
DA - 2026/10/27
JO - Nature Communications
DO - 10.1038/s41467-026-79159-4
UR - https://www.nature.com/articles/s41467-026-79159-4
AB - Klebsiella pneumoniae is a leading cause of neonatal sepsis in low- and middle-income countries and is increasingly multi-drug resistant, highlighting the need for vaccines. Putative vaccine targets include the lipopolysaccharide (O antigen) and capsular polysaccharide (K antigen), but capsule may mask O antigen and limit antibody-mediated opsonophagocytosis. We evaluated the activity of O antigen-specific antibodies induced by a tetravalent bioconjugate vaccine against 146 clinical isolates representing 17 prevalent capsule types associated with neonatal sepsis. Susceptibility to antibody-mediated killing varied by capsule type: four were consistently susceptible, six showed heterogeneous responses, and seven were resistant despite remaining susceptible to K antigen-specific antibodies. Killing of susceptible strains was predominantly mediated by anti-O1 antibodies, as demonstrated by competitive inhibition with purified polysaccharides. Collectively, these findings support an antigen-sparing vaccine design strategy, in which susceptible capsule types may be replaced by a single O type, reducing vaccine complexity while maintaining broad functional coverage.
SN - 2041-1723
ER -