ArticleVirulence2017
Endotoxin neutralization by an O-antigen specific monoclonal antibody: A potential novel therapeutic approach against Klebsiella pneumoniae ST258.
Article in Virulence, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 51 citations in OpenAlex.
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- O2a O-antigen type and sepsis in invasiveFrontiers in cellular and infection microbiology · 2026Article
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- Heptavalent O-Antigen Bioconjugate Vaccine Exhibiting Differential Functional Antibody Responses Against Diverse Klebsiella pneumoniae Isolates.The Journal of infectious diseases · 2024Article
- Klebsiella pneumoniae O-polysaccharide biosynthesis highlights the diverse organization of catalytic modules in ABC transporter-dependent glycan assembly.The Journal of biological chemistry · 2024Article
- Vaccines and Monoclonal Antibodies as Alternative Strategies to Antibiotics to Fight Antimicrobial Resistance.International journal of molecular sciences · 2024Review
- A heptavalent O-antigen bioconjugate vaccine exhibits differential functional antibody responses against diversebioRxiv : the preprint server for biology · 2023Article
- Identification of a second glycoform of the clinically prevalent O1 antigen fromProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Outsmarting Pathogens with Antibody Engineering.Annual review of chemical and biomolecular engineering · 2023Review
- Global, regional, and national estimates of the impact of a maternal Klebsiella pneumoniae vaccine: A Bayesian modeling analysis.PLoS medicine · 2023Article
- Genomic Analysis ofAntibiotics (Basel, Switzerland) · 2022Article
- Anti-bacterial monoclonal antibodies: next generation therapy against superbugs.Applied microbiology and biotechnology · 2022Review
- Anthocyanin Extract from Purple Sweet Potato Exacerbate Mitophagy to Ameliorate Pyroptosis inInternational journal of molecular sciences · 2021Article
- Prophylaxis and Treatment againstInternational journal of molecular sciences · 2021Review
- The Impact of Insertion Sequences on O-Serotype Phenotype and Its O-Locus-Based Prediction inInternational journal of molecular sciences · 2020Article
- Antibacterial Drug Development: A New Approach Is Needed for the Field to Survive and Thrive.Antibiotics (Basel, Switzerland) · 2020Article
- A bifunctional O-antigen polymerase structure reveals a new glycosyltransferase family.Nature chemical biology · 2020Article
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11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Klebsiella pneumoniae ST258 is a globally distributed multi-drug resistant pathogen responsible for severe invasive infections. In this study, the different virulence potential of K. pneumoniae ST258 isolates in endotoxin susceptible versus resistant animal models was shown. Furthermore, ST258 clinical isolates were found highly sensitive to the bactericidal effect of naive animal and human serum. These observations imply that LPS, released from the rapidly lysed bacteria, may contribute to the high mortality associated with ST258 bacteremia cases. A humanized version (mAb A1102) of a previously described murine mAb specific for the conserved LPS O-antigen, was tested for endotoxin neutralization. A1102 was able to neutralize TLR-4 activation by ST258-derived LPS in vitro with an efficacy exceeding that of polymyxin B by 3 orders of magnitude. Passive immunization with A1102 afforded a significant level of protection in a galactosamine-sensitized mouse model of endotoxemia, induced by ST258-derived LPS, or upon challenge with live bacteria. Efficacy was retained using an aglycosylated IgG, as well as upon complement depletion, suggesting that Fc-independent endotoxin neutralization may be the main protective mechanism in this model, in spite of the complement-dependent bactericidal and opsonic activities additionally observed for A1102 in vitro. Furthermore, rabbits that are naturally highly susceptible to endotoxin, were also significantly protected by low doses of A1102 when challenged with an ST258 strain. Given this unique mode of action and the high protective efficacy of this mAb, passive immunization, as prophylactic or adjunct therapeutic approach for the treatment of infections caused by ST258 isolates should be considered.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.