ArticleAntimicrobial agents and chemotherapy2010
Preclinical in vitro and in vivo characterization of the fully human monoclonal IgM antibody KBPA101 specific for Pseudomonas aeruginosa serotype IATS-O11.
Article in Antimicrobial agents and chemotherapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 55 citations in OpenAlex.
- IRAK-4 and MyD88 deficiencies impair IgM responses against T-independent bacterial antigens.Blood · 2014Trial
- Assessment of panobacumab as adjunctive immunotherapy for the treatment of nosocomial Pseudomonas aeruginosa pneumonia.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2014Trial
- Outsmarting Pathogens with Antibody Engineering.Annual review of chemical and biomolecular engineering · 2023Review
- Monoclonal antibodies against lipopolysaccharide protect againstFrontiers in cellular and infection microbiology · 2023Article
- IgM-enriched immunoglobulin improves colistin efficacy in a pneumonia model byLife science alliance · 2022Article
- Microbiome Modulation as a Novel Strategy to Treat and Prevent Respiratory Infections.Antibiotics (Basel, Switzerland) · 2022Review
- Molecular Mechanisms Involved in Pseudomonas aeruginosa Bacteremia.Advances in experimental medicine and biology · 2022Review
- Virulence Factors ofFrontiers in cellular and infection microbiology · 2022Review
- Defining the Mechanistic Correlates of Protection Conferred by Whole-Cell Vaccination against Pseudomonas aeruginosa Acute Murine Pneumonia.Infection and immunity · 2021Article
- Drug Prevention and Control of Ventilator-Associated Pneumonia.Frontiers in pharmacology · 2019Review
- Principles of Immunotherapy: Implications for Treatment Strategies in Cancer and Infectious Diseases.Frontiers in microbiology · 2018Review
- Targeting the gram-negative bacteria peptidoglycan synthase MraY as a new approach for monoclonal antibody anti-bacterial activity.Human vaccines & immunotherapeutics · 2017Article
- Pangenome-wide and molecular evolution analyses of the Pseudomonas aeruginosa species.BMC genomics · 2016Article
- Introduction of germline residues improves the stability of anti-HIV mAb 2G12-IgM.Biochimica et biophysica acta · 2015Article
- A Microarray-Matrix-assisted Laser Desorption/Ionization-Mass Spectrometry Approach for Site-specific Protein N-glycosylation Analysis, as Demonstrated for Human Serum Immunoglobulin M (IgM).Molecular & cellular proteomics : MCP · 2015Article
- Evaluating the bottlenecks of recombinant IgM production in mammalian cells.Cytotechnology · 2015Article
- A novel anti-PcrV antibody providing enhanced protection against Pseudomonas aeruginosa in multiple animal infection models.Antimicrobial agents and chemotherapy · 2014Article
- Expression and glycoengineering of functionally active heteromultimeric IgM in plants.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Vaccines for Pseudomonas aeruginosa: a long and winding road.Expert review of vaccines · 2014Review
- Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pseudomonas aeruginosa infection in ventilator-associated pneumonia is a serious and often life-threatening complication in intensive care unit patients, and new treatment options are needed. We used B-cell-enriched peripheral blood lymphocytes from a volunteer immunized with a P. aeruginosa O-polysaccharide-toxin A conjugate vaccine to generate human hybridoma cell lines producing monoclonal antibodies specific for individual P. aeruginosa lipopolysaccharide serotypes. The fully human monoclonal antibody secreted by one of these lines, KBPA101, is an IgM/kappa antibody that binds P. aeruginosa of International Antigenic Typing System (IATS) serotype O11 with high avidity (5.81 x 10(7) M(-1) +/- 2.8 x 10(7) M(-1)) without cross-reacting with other serotypes. KBPA101 specifically opsonized the P. aeruginosa of IATS O11 serotype and mediated complement-dependent phagocytosis in vitro by the human monocyte-like cell line HL-60 at a very low concentration (half-maximal phagocytosis at 0.16 ng/ml). In vivo evaluation of KBPA101 demonstrated a dose-response relationship for protection against systemic infections in a murine burn wound sepsis model, where 70 to 100% of animals were protected against lethal challenges with P. aeruginosa at doses as low as 5 microg/animal. Furthermore, a high efficacy of KBPA101 in protection from local respiratory infections in an acute lung infection model in mice was demonstrated. Preclinical toxicology evaluation on human tissue, in rabbits, and in mice did not indicate any toxicity of KBPA101. Based on these preclinical findings, the first human clinical trials have been initiated.
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