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Anti-bacterial Monoclonal Antibodies

  • Eszter Nagy
  • Gábor Nagy
  • Christine A. Power
  • Adriana Badarau
  • Valéria Szijártó
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1053)

Abstract

The failing efficacy of antibiotics and the high mortality rate among high-risk patients calls for new treatment modalities for bacterial infections. Due to the vastly divergent pathogenesis of human pathogens, each microbe requires a tailored approach. The main modes of action of anti-bacterial antibodies are virulence factor neutralization, complement-mediated bacterial lysis and enhancement of opsonophagocytic uptake and killing (OPK). Gram-positive bacteria cannot be lysed by complement and their pathogenesis often involves secreted toxins, therefore typically toxin-neutralization and OPK activity are required to prevent and ameliorate disease. In fact, the success stories in terms of approved products, in the anti-bacterial mAb field are based on toxin neutralization (Bacillus anthracis, Clostridium difficile). In contrast, Gram-negative bacteria are vulnerable to antibody-dependent complement-mediated lysis, while their pathogenesis rarely relies on secreted exotoxins, and involves the pro-inflammatory endotoxin (lipopolysaccharide). Given the complexity of bacterial pathogenesis, antibody therapeutics are expected to be most efficient upon targeting more than one virulence factor and/or combining different modes of action. The improved understanding of bacterial pathogenesis combined with the versatility and maturity of antibody discovery technologies available today are pivotal for the design of novel anti-bacterial therapeutics. The intensified research generating promising proof-of-concept data, and the increasing number of clinical programs with anti-bacterial mAbs, indicate that the field is ready to fulfill its promise in the coming years.

Keywords

Microbial pathogenesis Antibody targets Toxin neutralization Bactericidal antibodies Passive immunization 

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2017

Authors and Affiliations

  • Eszter Nagy
    • 1
  • Gábor Nagy
    • 1
  • Christine A. Power
    • 1
  • Adriana Badarau
    • 1
  • Valéria Szijártó
    • 1
  1. 1.Arsanis Biosciences GmbH/Arsanis, IncViennaAustria

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