Passive antibody therapy for infectious diseases

Abstract

Passive antibody therapy is not a new technique. Behring and Kitasato discovered that specific antibodies could protect against bacterial toxins in the early 1890s and, by the 1930s, serum therapy was being widely used to treat a variety of infectious diseases. However, the increase in the popularity of serum therapy occurred at about the same time as the first antibiotics were developed, and as antibiotics became more widely available, so the use of serum therapy declined. By the late 1940s it had largely been abandoned. In recent years there has been renewed interest in using passive antibody therapy to treat infectious diseases. However, at present, although immunoglobulin preparations are available to treat some infections, such as hepatitis B, rabies and varicella–zoster virus, only one monoclonal antibody (palivizumab) has been licensed to prevent an infectious disease. The advantages of using antibody molecules to treat infectious diseases include their specificity and versatility. Antibodies are capable of mediating a variety of different biological effects including both those that are independent of other components of the host immune system, such as neutralizing toxins and viruses and activating complement, and effects that involve other components of the host immune system, such as antibody-dependent cellular cytotoxicity and opsonization. Additionally, the effects of antibodies can be synergistic with those of conventional antimicrobial therapies, and the time to develop therapeutic antibody preparations would be considerably shorter than the development time for a vaccine. One of the most important advantages of using antibodies is that they can be easily modified to target host cells. One such strategy is radioimmunotherapy, in which a radionuclide is attached to an antibody molecule. As an intact immune system is not required, radioimmunotherapy could be particularly effective in immunocompromised hosts. As infected cells can be killed by a 'crossfire' effect, radioimmunotherapy might also be useful to target intracellular pathogens and chronic infections. The high specificity of antibodies can also be a disadvantage when considering antibody-based therapies because accurate diagnosis of the causative microbial agent of an infection is necessary and a 'cocktail' of different antibodies might be required to treat infections with a microorganism that undergoes antigenic variation. As the efficacy of therapeutic antibody preparations decreases with time, this might mean that they are best applied to infections where early diagnosis is possible. Additionally, the costs associated with antibody treatments can be higher than treatment with conventional antimicrobial agents; however, the increased costs of the treatment should be offset against the lower rates of resistance associated with antibody therapy.