Genomic characterization of global Klebsiella pneumoniae bloodstream infection isolates:  a systematic review and insights into potential vaccine candidates

2026 · doi:10.1099/acmi.0.001234.v1
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This study is a systematic review using whole-genome sequencing of 1,076 Klebsiella pneumoniae bloodstream infection isolates to evaluate vaccine antigen coverage targeting capsule K-types and lipopolysaccharide (LPS) O-antigens, along with antimicrobial resistance and hypervirulence markers. Using Kleborate for K- and O-typing and annotation tools (Prokka, Roary, PSORTb) plus antigenicity prediction software (VaxiJen and ANTIGENpro), the authors report that 80.8% of isolates exhibited AMR and 8.4% were hypervirulent, with substantial antigenic diversity requiring multiple K-types for partial polysaccharide vaccine coverage (~70% with at least 20 K-types). Predicted multivalent formulations ranged from ~46.6% coverage for a K1/K2-focused hypervirulence-targeting vaccine up to 90–94% for expanded O-type combinations, and they identified 85 core outer membrane proteins present in most strains with 65 predicted as probable antigens. The paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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Abstract

Background: Vaccination would be an effective way to prevent infections caused by Klebsiella pneumoniae, including strains with antimicrobial resistance (AMR) and hypervirulence. Selecting antigens with broad coverage is key for this highly variable pathogen. We assessed the potential coverage for vaccines based on the capsule K- and lipopolysaccharide (LPS) O-antigens by whole-genome sequence (WGS) analysis of 1,076 K. pneumoniae isolates from bloodstream infections. We identified surface-exposed proteins with predicted broad coverage and antigenicity. Methods We conducted a systematic review to identify published whole-genome sequence data of K. pneumoniae bloodstream isolates. Kleborate was used to determine K- and O-types, AMR, and hypermucoid-associated genes. Draft assemblies were annotated with Prokka, and Roary was used to investigate the pangenome with core genes (present in ≥80% strains). PSORTb was used to determine the proteins subcellular localization and antigenicity was predicted using VaxiJen and ANTIGENpro. Results A total of 94 studies were included in the systematic review, and involved adults (³18 years old), mixed age groups (0 – 96 years old), and young infant (0 -74 days) populations. WGS analysis showed that 80.8% of isolates exhibited AMR and 8.4% had hypervirulence. At least 20 K-types would need to be included in a polysaccharide-based vaccine to achieve ~70% coverage. The K1/K2- bioconjugate vaccine targeting hypervirulent strains had a predicted coverage of 46.6% of all hypervirulent K. pneumoniae, while expanding the valency to include K57 and K64 could increase coverage to 77.2%. The Kleb4V vaccine (which includes O-types O1, O2a, O2afg, and O3b) had an estimated coverage of 83.9%, and incorporating O4 and O5 types could increase coverage to 90-94%. A different quadrivalent conjugate vaccine had an estimated coverage of 88.4%, and could increase coverage to 96.3% by including O4. There were 85 core outer membrane proteins (OMPs) present in 83-99% of all strains, of which 65 were predicted as probable antigens by both VaxiJen and ANTIGENpro tools. Conclusions These data indicate the challenges in developing a broadly protective K. pneumoniae vaccine, and the potential coverage of different formulations, providing a foundation for future vaccine development.
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Abstract

Background: Vaccination would be an effective way to prevent infections caused by Klebsiella pneumoniae, including strains with antimicrobial resistance (AMR) and hypervirulence. Selecting antigens with broad coverage is key for this highly variable pathogen. We assessed the potential coverage for vaccines based on the capsule K- and lipopolysaccharide (LPS) O-antigens by whole-genome sequence (WGS) analysis of 1,076 K. pneumoniae isolates from bloodstream infections. We identified surface-exposed proteins with predicted broad coverage and antigenicity.

Methods

We conducted a systematic review to identify published whole-genome sequence data of K. pneumoniae bloodstream isolates. Kleborate was used to determine K- and O-types, AMR, and hypermucoid-associated genes. Draft assemblies were annotated with Prokka, and Roary was used to investigate the pangenome with core genes (present in ≥80% strains). PSORTb was used to determine the proteins subcellular localization and antigenicity was predicted using VaxiJen and ANTIGENpro.

Results

A total of 94 studies were included in the systematic review, and involved adults (³18 years old), mixed age groups (0 – 96 years old), and young infant (0 -74 days) populations. WGS analysis showed that 80.8% of isolates exhibited AMR and 8.4% had hypervirulence. At least 20 K-types would need to be included in a polysaccharide-based vaccine to achieve ~70% coverage. The K1/K2- bioconjugate vaccine targeting hypervirulent strains had a predicted coverage of 46.6% of all hypervirulent K. pneumoniae, while expanding the valency to include K57 and K64 could increase coverage to 77.2%. The Kleb4V vaccine (which includes O-types O1, O2a, O2afg, and O3b) had an estimated coverage of 83.9%, and incorporating O4 and O5 types could increase coverage to 90-94%. A different quadrivalent conjugate vaccine had an estimated coverage of 88.4%, and could increase coverage to 96.3% by including O4. There were 85 core outer membrane proteins (OMPs) present in 83-99% of all strains, of which 65 were predicted as probable antigens by both VaxiJen and ANTIGENpro tools.

Conclusions

These data indicate the challenges in developing a broadly protective K. pneumoniae vaccine, and the potential coverage of different formulations, providing a foundation for future vaccine development. - Received: - Version Posted: Funding - BC Children's Hospital - Principal Award Recipient: Manish Sadarangani

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