Monoclonal antibody-based therapies for bacterial infections

Abstract

Purpose of review-This review highlights recent developments in the development of monoclonal antibodies to treat bacterial disease, including preclinical advances and the status of current clinical trials. Recent Findings-Monoclonal antibody (mAb) therapy is becoming increasingly promising in the infectious disease field. Though bacterial exotoxins continue to be a mainstay of mAb targets, searches for protein targets on the surface of bacteria have uncovered new mechanisms of antibody-mediated action against bacteria. Additionally, surveys of the polysaccharide serotype prevalence among antibiotic resistant bacterial populations have yielded opportunities to leverage human selective pressures to our clinical advantage. Several mAb candidates are progressing through clinical development with great promise, especially those with structures altered to provide maximum benefit. While other clinical trials have recently proved unsuccessful, these failures and lessons from immune profiling provide opportunities to understand how vulnerabilities of certain targets may change in different disease states. Summary-Despite the hurdles of identifying effective targets and understanding how mAbs provide protection within different infections, we show that the progress made in these fields is a positive indication of mAbs becoming more widely accepted as the future for treating bacterial infections.

Renaissance of vancomycin: approaches for breaking antibiotic resistance in multidrug-resistant bacteria

“…Instead of developing new antibiotics that address novel targets, current approaches focus on structural modifications of well-established antibiotics such as vancomycin to restore their impact on resistant bacteria. Various further strategies to combat lifethreatening bacterial infections, such as the use of bacteriophages (Matsuzaki et al 2005), monoclonal antibodies (Lorenz et al 2000;Motley et al 2019), antimicrobial peptides (Fox 2013), metallic and polymeric nanoparticles (Beyth et al 2015), and quorum-sensing inhibitors (Rasmussen and Givskov 2006), among others, are under extensive investigation (Simões et al 2017). However, despite partially suggesting promising potential as effective alternative antimicrobials, to date, none of these novel strategies have found significant broad application.…”

Lysophosphatidic acid (LPA)-antibody (504B3) engagement detected by interferometry identifies off-target binding

“…The anti-LPA antibody, 504B3, binds other lipids beyond LPA. The use of antibody-based therapies has produced multiple therapeutic successes, ranging from cancer to autoimmune and infectious diseases [ 30 – 33 ], with the majority targeting protein epitopes. By contrast, bioactive lipids present more challenging targets in that they have overlapping epitopes, are present within most if not all cell membranes (e.g.…”

A Predictive Model of Antibody Binding in the Presence of IgG-Interacting Bacterial Surface Proteins

“…Monoclonal antibody treatments have shown potential for a wide spectrum of disease. Despite this, there are very few monoclonal antibodies (mAbs) clinically available for treatment of bacterial infections ( 10 , 11 ). Furthermore, pooled human IgG is used clinically for treatment of certain invasive GAS infections, but studies show no clear effect of this treatment ( 12 – 15 ).…”