Related Experiment Video
Updated: Jan 11, 2026
Production of Monoclonal Antibodies Targeting Aminopeptidase N in the Porcine Intestinal Mucosal Epithelium
Published on: May 18, 2021
EPY001, a Novel Monoclonal Antibody Against Pseudomonas aeruginosa Targeting OprF
Guillaume Lacroix1,2, Jean-Luc Lenormand3
1Epynext Therapeutics, 38000 Grenoble, France.
Abstract:
Pseudomonas aeruginosa (P. aeruginosa) is a high-priority opportunistic pathogen responsible for severe healthcare-associated infections exhibiting multidrug resistance, emphasizing the urgent need for alternative therapeutic strategies. Monoclonal antibodies (mAbs) targeting the highly conserved outer membrane protein OprF represent a promising approach to mitigate its infectivity. OprF, the major and highly conserved outer membrane protein of P. aeruginosa, plays key roles in the pathogenesis of this bacterium, including biofilm formation, host cell adhesion, immune sensing, and resistance to macrophage clearance, making it a crucial factor in virulence and a promising immunotherapeutic target. Here, we report the preclinical evaluation of EPY001, an anti-OprF mAb generated by immunization of a macaque with OprF-containing proteoliposomes. EPY001 exhibited strong nanomolar binding to OprF. Epitope mapping suggests recognition of a conformational epitope, underscoring the value of proteoliposome-based immunization for membrane protein targets. Functional assays provide insights into OprF's role in biofilm formation, pyocyanin production, and antibiotic resistance. However, in vivo studies revealed that targeting OprF alone is insufficient to protect mice from lethal infection. These findings contribute to ongoing efforts to develop effective alternatives to conventional antibiotics against this resilient pathogen.
Insights
A new monoclonal antibody (mAb) targeting Pseudomonas aeruginosa
Area of Science:
- Microbiology
- Immunology
- Infectious Diseases
Background:
- Pseudomonas aeruginosa is a high-priority pathogen causing severe healthcare-associated infections.
- Multidrug resistance in P. aeruginosa necessitates alternative therapeutic strategies.
- The outer membrane protein OprF is crucial for P. aeruginosa virulence and a potential immunotherapeutic target.
Purpose of the Study:
- To evaluate the preclinical efficacy of EPY001, a novel anti-OprF monoclonal antibody.
- To investigate the role of OprF in P. aeruginosa pathogenesis.
- To explore OprF as a target for combating antibiotic-resistant infections.
Main Methods:
- Generation of anti-OprF mAb (EPY001) via macaque immunization with proteoliposomes.
- Characterization of EPY001 binding affinity and epitope recognition.
- Assessment of OprF's role in biofilm formation, pyocyanin production, and antibiotic resistance through functional assays.
- Evaluation of EPY001 efficacy in a murine model of P. aeruginosa infection.
Main Results:
- EPY001 demonstrated strong nanomolar binding to OprF, recognizing a conformational epitope.
- Functional assays revealed OprF's involvement in biofilm formation, pyocyanin production, and antibiotic resistance.
- In vivo studies indicated that targeting OprF alone was insufficient to protect against lethal P. aeruginosa infection.
Conclusions:
- EPY001 shows promise as a therapeutic candidate targeting OprF.
- OprF plays a significant role in P. aeruginosa virulence.
- Further strategies may be needed to enhance the efficacy of anti-OprF therapies against severe P. aeruginosa infections.
