Cross-specificity of protective human antibodies against Klebsiella pneumoniae LPS O-antigen

Nature Immunology
Tim RollenskeHedda Wardemann

Abstract

Humoral immune responses to microbial polysaccharide surface antigens can prevent bacterial infection but are typically strain specific and fail to mediate broad protection against different serotypes. Here we describe a panel of affinity-matured monoclonal human antibodies from peripheral blood immunoglobulin M-positive (IgM+) and IgA+ memory B cells and clonally related intestinal plasmablasts, directed against the lipopolysaccharide (LPS) O-antigen of Klebsiella pneumoniae, an opportunistic pathogen and major cause of antibiotic-resistant nosocomial infections. The antibodies showed distinct patterns of in vivo cross-specificity and protection against different clinically relevant K. pneumoniae serotypes. However, cross-specificity was not limited to K. pneumoniae, as K. pneumoniae-specific antibodies recognized diverse intestinal microbes and neutralized not only K. pneumoniae LPS but also non-K. pneumoniae LPS. Our data suggest that the recognition of minimal glycan epitopes abundantly expressed on microbial surfaces might serve as an efficient humoral immunological mechanism to control invading pathogens and the large diversity of the human microbiota with a limited set of cross-specific antibodies.

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Datasets Mentioned

BETA
DB-5989

Methods Mentioned

BETA
Serotyping
flow cytometry
enzyme-linked immunosorbent assay
ELISA
surface plasmon resonance
gel filtration
density-gradient centrifugation
FCS
PCR
ELISAs

Software Mentioned

IgBlast
FlowJo
gplots
pandaseq
Photoshop
R
QIIME
Adobe
circlize
MALDI BioTyper

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