Anti-infective Antibodies

Pseudomonas aeruginosa is an opportunistic bacterial pathogen which causes life-threatening infections in immunocompromised individuals. Multi-drug resistant strains of P. aeruginosa are notorious amongst clinicians and resistance development is mainly associated with the ability of this bacterium to grow in a polysaccharide matrix called 'biofilms', which become impenetrable to the components of the immune system and conventional antibiotics.There is an urgent clinical and commercial need to develop novel strategies to prevent these infections.

A number of Gram negative bacteria including P. aeruginosa utilise cell-cell communication or quorum sensing (QS) to control the expression of major virulence factors and biofilm formation. Targeting virulence rather than bactericidal or bacteriostatic strategies are less likely to induce selective pressure for the development of resistant strains. Therefore we have developed a novel strategy of infection control byblocking (or immuno-modulation) cell-to-cell communication by monoclonal antibodies. By constructing an immunised antibody library and employing phage display technology, we have isolated high sensitivity (nM range) monoclonal antibodies against homoserine lactones (HSLs), which are a class of compounds extremely challenging to raise antibodies against due to their inherent lack of key antigenic properties.  In addition, these antibodies are cross-reactive to related QS compounds utilised by other G-ve bacterial species such as Acinetobacter baumannii and Klebsiella pnemoniae.

Anti-HSL antibodies are currently undergoing animal studies in murine lung infection models, which would generate early stage proof-of-concept data to demonstrate the potential of HSL-specific, monoclonal antibodies as clinical leads suitable for the prevention or treatment of life-threatening, bacterial infections. In order to explore the diagnostic potential of these high sensitivity antibodies, we are developing a point-of-care diagnostic kit for the rapid detection and differentiation of pathogens involved in sepsis and other catheter associated localised infections.  

Project Team – Prof Andy Porter, Dr Soumya Palliyil

Project Funding – Knowledge Transfer Partnerships, Knowledge Exchange and Transfer, SULSA