Building upon our previous research, the German Center for Infection Research (Deutsches Zentrum für Infektionsforschung, DZIF) has awarded €1.7 million to support the continued development of our human anti-PcrV monoclonal antibodies over the next three years. These antibodies are designed to specifically inhibit the type III secretion system of Pseudomonas aeruginosa, a critical mechanism involved in severe bacterial infections. Targeted blocking of this secretion system represents a promising and innovative therapeutic strategy against P. aeruginosa infections, independent of antibiotic resistance.
In preclinical studies, our human-derived antibodies have demonstrated superior efficacy compared to all existing antibody candidates, which primarily originate from mouse immunization. Unlike conventional antimicrobial agents, antibodies exhibit an extended plasma half-life, maintaining therapeutic plasma levels for weeks after administration. This characteristic enables antibodies to be employed not only for therapeutic purposes but also prophylactically to prevent infections through passive immunization.
Moreover, human therapeutic antibodies are known for their highly favorable safety profile, with severe adverse events being exceedingly rare. This funding from DZIF highlights the significant potential of our antibodies to provide effective, safe, and long-lasting solutions in the fight against antibiotic-resistant bacterial infections.
An important milestone of this funded project will be the selection of an antibody candidate and its initial production under Good Manufacturing Practice conditions. Based on these efforts, future clinical studies are planned involving patients with acute P. aeruginosa infections.
A big congratulations to Sara for winning the poster prize at the annual meeting of the German Center for Infection Research (DZIF) and the German Society for Infectious Diseases (DGI) in Munich!
Three new members have joined our lab to further explore novel therapeutic strategies against bacterial infections. We wish you a great start and much success in your efforts!
If you're interested in our workflow for producing Pseudomonas aeruginosa type III secretion system-neutralizing monoclonal antibodies from human B cells, a detailed protocol is now available.
Antibiotic-resistant bacteria represent an escalating global threat, impacting not only those affected but also straining entire healthcare systems. In particular, infections with the bacterium Pseudomonas aeruginosa are feared due to numerous resistance mechanisms and can lead to complicated lung and bloodstream infections, especially in critically ill individuals. Furthermore, this pathogen has the capability to colonize organs like the lungs, contributing to progressive tissue damage.
In our study, we explored the potential of isolating and expressing highly neutralizing antibodies from human immune cells - a successful strategy for viral infections - to develop novel therapies for bacterial infections. Our focus was on determining whether this approach, proven effective in viral contexts, could be extended to combat bacterial infections. To identify suitable antibodies, we concentrated on patients with cystic fibrosis, a condition often associated with chronic P. aeruginosa colonization in the lungs. Through screening assays, we identified monoclonal antibodies in the blood samples of certain cystic fibrosis patients capable of neutralizing P. aeruginosa's virulence.
These antibodies operate by blocking a crucial virulence factor of the bacterium—the type III secretion system, which plays an important role especially in severe infections with P. aeruginosa. Extensive experiments involving cell culture and animal models demonstrated that the newly developed antibodies exhibit efficacy comparable to classical antibiotics against the bacterium. Notably, these antibodies, remain effective against highly resistant bacteria, as their activity is independent of the mechanisms employed by conventional antibiotics.
Congrats to Alexandra for winning the poster prize at the annual meeting of the German Center for Infection Research (DZIF) in Hannover! Well done!
