Antibody-Based Therapies in Infectious Diseases
Before antibiotics, sera from immune animals and humans were used to treat a variety of infectious diseases, often with successful results. In the beginning of the 20th century, serum therapy had taken a place in standard treatment protocols for several i
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11 Antibody-Based Therapies in Infectious Diseases H. Barbaros Oral and Cezmi A. Akdis˛ 1. Introduction Before antibiotics, sera from immune animals and humans were used to treat a variety of infectious diseases, often with successful results. In the beginning of the 20th century, serum therapy had taken a place in standard treatment protocols for several infectious diseases, such as meningitis, diphtheria, tetanus, and lobar pneumonia. As early as 1906, antimeningococcal serum was intravenously used as a treatment for meningitis, since it was proved to cross the blood–brain barrier. However, treatment with meningococcal antiserum was shown to be ineffective, because available antiserum was only effective against type A meningococcus, whereas type C was a more common cause of meningococcal meningitis (1). Several trials demonstrated that application of type-specific antipneumococcal serum reduced mortality in patients with lobar pneumonia by about 50%, from 30–40% to 10–20% (2). Several successes with immune serum were observed in treatment and prevention of other infectious diseases, which include Haemophilus influenzae meningitis, measles, diphtheria, hepatitis A and B, poliovirus infection, and cytomegalovirus (CMV) infection (1). However, numerous problems have been observed with immune sera, including lot-to-lot variations characterized with variable amounts of specific antibodies, occurrence of serum sickness as a complication, and some hazards in transmission of some infectious diseases (3,4). After the discovery of antimicrobial chemotherapy in the mid-1930s, serum therapy for some bacterial infections was rapidly forsaken (5). However, today antibody-based therapy for infectious diseases is still routinely used in few situations, including replacement therapy in patients with immunodeficiency, prophylaxis against various viruses (rabies, measles, hepatitis A and B, varicella, mumps, cytomegalovirus) following exposure, and toxin neutralization (diphtheria, tetanus, and botulism). From: Methods in Molecular Medicine, Vol. 40: Diagnostic and Therapeutic Antibodies Edited by: A. J. T. George and C. E. Urch © Humana Press Inc., Totowa, NJ
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In the last two decades, problems with treatment of newly emerged, re-emerged, or persistent infectious diseases necessitated researchers to develop new and/or improved immune therapeutic approaches. The development of monoclonal antibody (mAb) technology by Köhler and Milstein was the most important forward step in this area (6). Since then, mAbs have been used for diagnostic purposes and they are applicable to immunotherapy of human diseases. They have been applied clinically against various specific microorganisms, such as Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa, CMV, Varicella Zoster Virus (VZV), and Respiratory Syncytial Virus (RSV) (7,8). In several multicenter clinical trials, mAbs raised against specific epitopes or cellular components of microorganisms, against microorganisms themselves, or against some host fa
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