Monoclonal Antibodies Targeting Surface-Exposed and Secreted Proteins from Staphylococci

Abstract

Staphylococci (specifically Staphylococcus aureus and Staphylococcus epidermidis) are the causative agents of diseases ranging from superficial skin and soft tissue infections to severe conditions such as fatal pneumonia, bacteremia, sepsis and endocarditis. The widespread and indiscriminate use of antibiotics has led to serious problems of resistance to staphylococcal disease and has generated a renewed interest in alternative therapeutic agents such as vaccines and antibodies. Staphylococci express a large repertoire of surface and secreted virulence factors, which provide mechanisms (adhesion, invasion and biofilm development among others) for both bacterial survival in the host and evasion from innate and adaptive immunity. Consequently, the development of antibodies that target specific antigens would provide an effective protective strategy against staphylococcal infections. In this review, we report an update on efforts to develop anti-staphylococci monoclonal antibodies (and their derivatives: minibodies, antibody–antibiotic conjugates) and the mechanism by which such antibodies can help fight infections. We also provide an overview of mAbs used in clinical trials and highlight their therapeutic potential in various infectious contexts.

Antigenic landscapes on Staphylococcus aureus pore-forming toxins reveal insights into specificity and cross-neutralization

“…Several antibodies described in the literature such as MEDI4893 and ASN100 that are specific to neutralizing Hla toxicity by targeting the rim domain and involved in blocking the assembly of a heptameric complex of destabilization 20 at the pre-pore stage are currently in clinical trials. 56 Although the rim is a critical site for toxin neutralization, using mAbs 2B6 and CAN6 we identified two new epitopes that mediate potent neutralization of Hla. We showed that 2B6 targets a linear epitope near the amino latch of Hla at the N-terminal region that undergoes a conformational change and allows the ß-barrel pore formation from the pre-pore form.…”

Staphylococcus aureus—A Known Opponent against Host Defense Mechanisms and Vaccine Development—Do We Still Have a Chance to Win?

“…As the world rightly focuses on limiting the spread of COVID-19, the current pandemic situation has exposed our vulnerability to the infections for which there are no effective vaccines or treatments [105,106]. An integrated strategy that includes multitargeted vaccines together with modern diagnostic tools, novel antibiotics, monoclonal antibodies, microbiota modulation, as well as the use of antimicrobial peptides, bacteriocins, plantderived products and bacteriophages are required to combat AMR effectively [119][120][121][122][123][124]. The still-developing research trend concerning interference with the expression of pathogen virulence factors at the molecular and submolecular levels is also very important.…”

Cyanidin chloride protects mice from methicillin-resistant Staphylococcus aureus-induced pneumonia by targeting Sortase A

“…MRSA itself expresses many surface proteins and secretes different virulence factors, which provides mechanisms for bacteria to survive and escape from innate and adaptive immunity (adhesion, invasion, biofilm formation, etc.) [ 8 ]. Therefore, developing a screen for specific virulence factor inhibitors will provide an effective therapeutic strategy for MRSA infection.…”