Monoclonal Antibodies for Bacterial Pathogens: Mechanisms of Action and Engineering Approaches for Enhanced Effector Functions

Abstract

Monoclonal antibody (mAb) therapy has opened a new era in the pharmaceutical field, finding application in various areas of research, from cancer to infectious diseases. The IgG isoform is the most used therapeutic, given its long half-life, high serum abundance, and most importantly, the presence of the Fc domain, which can be easily engineered. In the infectious diseases field, there has been a rising interest in mAbs research to counteract the emerging crisis of antibiotic resistance in bacteria. Various pathogens are acquiring resistance mechanisms, inhibiting any chance of success of antibiotics, and thus may become critically untreatable in the near future. Therefore, mAbs represent a new treatment option which may complement or even replace antibiotics. However, very few antibacterial mAbs have succeeded clinical trials, and until now, only three mAbs have been approved by the FDA. These failures highlight the need of improving the efficacy of mAb therapeutic activity, which can also be achieved with Fc engineering. In the first part of this review, we will describe the mechanisms of action of mAbs against bacteria, while in the second part, we will discuss the recent advances in antibody engineering to increase efficacy of pre-existing anti-bacterial mAbs.