Selection and development of a therapeutic antibody against drug-resistant Klebsiella pneumoniae

Purpose and goal

The purpose of the project was to identify antibodies with activity versus the bacterial species Klebsiella pneumoniae, both in in vitro and in vivo assays. The project did not reach its purpose, as manufactured B-cell supernatants did not show any evidence of binding to bacteria in in vitro assays. The project was finalised prematurely due to the lack of evidence of binding, which would not have made it meaningful to proceed to animal infection models.

Expected results and effects

We succeeded in establishing antibody assays for the bacterial species K. pneumoniae, including assays for cell cultures. However, one of the project partners manufactured B-cell supernatants that unfortunately did not show binding activity towards the strains used in the project. We developed a good understanding of challenges related to therapeutic antibodies versus K. pneumoniae - the thick capsule means strategies should be targeting also ways of depolymerising the capsule.

Planned approach and implementation

In this project, the partner responsible for manufacturing B-cell supernatants was acquired by another company, and following this the collaboration was problematic. Unfortunately, it was impossible to get working supernatants that could bind to the K. pneumoniae strains. We tried several types of trouble-shooting with a capsule-negative mutant, but the assays never worked. Our part of the project was executed as planned, but ultimately there were not supernatants with promising activity that could be used for epitope mapping, manufacturing, and finally in the animal model.