Antibodies as Anti-Infective Agents in Medicinal Chemistry

Jarbas   Rodrigues   de Oliveira; Fernanda   Bordignon   Nunes; Melissa   Guerra   Simoes Pires; Denizar Alberto   da   Silva Melo; Marcio   Vinicius   Fagundes Donadio

doi:10.2174/187152108785908811

Abstract

The treatment of infectious diseases has been complicated by the rising of new pathogens, the spread of antibiotic- resistant strains and the relative inefficacy of antimicrobial chemotherapy in immunocompromised hosts. This has led to renewed interest in the utilization of antibody-based therapies as anti-infective agents. Antibody-based therapies are effective against a wide variety of pathogens. In recent years they have become first-line therapy for a variety of conditions that include viral infections, inflammatory disorders, and certain malignancies. Renewed interest in antibody-based therapies is a consequence of major advances in antibody production technology and the need for new therapeutic agents. Dozens of antibody preparations are in clinical use. Several monoclonal antibodies (mAb) are now licensed for clinical use and many are in advanced clinical development. As a class, antibody-based therapies have significant advantages and disadvantages when compared to conventional antimicrobial chemotherapy. Advantages include versatility, specificity, and antimicrobial activities not available in antibiotic drugs, such as toxin and viral neutralization, opsonisation, complement activation and the enhancement of host immune function. Disadvantages include expense, the necessity for early and accurate diagnosis prior to use, and the complex logistics necessary for therapeutic use. Advances in antibody technology have minimized some of the disadvantages associated with antibody therapy. The recent spread of hybridoma technology among laboratories has promoted the development of mAb use against a wide variety of infectious disease agents. Monoclonal antibodies have in fact been used to identify new antigenic determinants in various microorganisms, to show antigenic differences between species, strains, types and development cycles and to reveal the existence of natural antigenic variants. While mAb theoretically represent an excellent (perhaps superior) alternative to conventional antisera as diagnostic, therapeutic or laboratory reagents, traditional antisera may be preferable to mAb in some circumstances because of its fixed affinity and specificity as well as the limited functional capacities of some antibodies. The acceptance of mAb by the clinical microbiologist and physician must await proof of their reliability, safety and efficacy. Continued success in the development of antibody-based therapies will require extensive clinical research to learn how to use these compounds optimally and immunological research to define the basic mechanisms of antibody action. Given the need for new antimicrobial therapies and many recent technological advances in the field of immunoglobulin research, there is considerable optimism regarding renewed applications of antibody-based therapy for the prevention and treatment of infectious diseases. In this paper, we review the applications of immune therapy for infectious diseases.

Keywords: Monoclonal antibodies, anti-infective, polyclonal antibodies, immune therapy, bacterial diseases, viral diseases, fungi infections

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