Deciphering the human B cell response to develop neutralizing antibodies against Enterococcus faecalis

• Applicant: Dr. Alexander Simonis
• Subject Area: Clinical Infectiology and Tropical Medicine
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 546139550

Nosocomial infections, defined as infections causally linked to medical interventions, pose an escalating threat to patients and present a significant challenge to our healthcare system. A common cause of these infections is Enterococcus faecalis, a Gram-positive bacterium naturally residing in the human intestinal flora. Particularly in immunocompromised or critically ill patients, this bacterium causes conditions such as bloodstream infections, urinary tract infections, as well as wound and intra-abdominal infections. Given its pivotal role as a leading cause of nosocomial infections, associated with substantial morbidity, mortality, and healthcare costs, there is an urgent call for innovative therapeutic and prophylactic strategies. A potential therapeutic approach in this context are anti-virulence therapies, which target selectively bacterial virulence factors. Monoclonal antibodies, in particular, present an attractive option for specifically binding and neutralizing extracellular virulence factors. This strategy has proven successful over the past two decades in combating viral infections. Many of these highly effective antibodies have been derived from human antigen-specific B cells following infection or vaccination. The objective of the proposed project is to extend this methodology to unravel the B cell response to E. faecalis virulence factors with the ultimate aim to develop highly neutralizing antibodies. In the initial phase, testing for virulence factor-specific and neutralizing antibodies will be conducted within a study cohort, followed by the analysis of the B cell repertoire at single-cell level from selected individuals. In addition to providing insights into the human immune response, these analyses enable the recombinant production of monoclonal antibodies, which can subsequently be evaluated for their effectiveness. The identification of highly potent neutralizing antibodies holds the potential to pioneer innovative antibody-based therapies for E. faecalis infections, ultimately mitigating the associated morbidity and mortality. Moreover, the extended half-life of antibodies allows for passive immunization, offering a protective measure for vulnerable patients.

• DFG Programme: Research Grants