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Passive antibody therapy for infectious diseases

Nature Reviews Microbiology volume 2, pages 695–703 (2004) Cite this article

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Key Points

  • 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.

Abstract

Antibody-based therapies are currently undergoing a renaissance. After being developed and then largely abandoned in the twentieth century, many antibody preparations are now in clinical use. However, most of the reagents that are available target non-infectious diseases. Interest in using antibodies to treat infectious diseases is now being fuelled by the wide dissemination of drug-resistant microorganisms, the emergence of new microorganisms, the relative inefficacy of antimicrobial drugs in immunocompromised hosts and the fact that antibody-based therapies are the only means to provide immediate immunity against biological weapons. 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.

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Figure 1: The different biological effects of antibodies.
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Figure 2: Cryptococcus neoformans infection and radioimmunotherapy.
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Figure 3: A schematic representation of the mechanisms by which radioimmunotherapy is effective against microorganisms.
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Acknowledgements

The authors would like to thank R. Bryan and T. Moadel for obtaining images of C. neoformans-infected animals.

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Authors and Affiliations

  1. Departments of Medicine (Division of Infectious Diseases) and Microbiology, Albert Einstein College of Medicine, Bronx, 10461, New York, USA

    Arturo Casadevall & Liise-anne Pirofski

  2. Department of Nuclear Medicine, Albert Einstein College of Medicine, Bronx, 10461, New York, USA

    Ekaterina Dadachova

Authors
  1. Arturo Casadevall
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  2. Ekaterina Dadachova
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Correspondence to Arturo Casadevall.

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DATABASES

Entrez

Bacillus anthracis

Clostridium botulinum

Clostridium tetani

Listeria monocytogenes

Mycobacterium tuberculosis

Streptococcus pneumoniae

Infectious Disease Information

Ebola virus

hepatitis A and B

HIV

respiratory syncytial virus

rabies

varicella–zoster virus

FURTHER INFORMATION

Arturo Casadevall's laboratory

Liise-anne Pirofski's laboratory

Ekaterina Dadachova's laboratory

Encyclopedia of Life Sciences

monoclonal antibodies: therapeutic uses

US Food and Drug Administration

Glossary

HYPERSENSITIVITY REACTION

An inappropriate reaction to an allergen that can be immediate (types I, II and III) or delayed (type IV). Different hypersensitivity reactions involve different antibody classes and effector cells.

ANTIGEN–ANTIBODY COMPLEX DISEASE

An immune complex disease that is caused by the administration of foreign serum or serum proteins, and is characterized by fever, lymphadenopathy and skin welts.

MONOCLONAL ANTIBODY

A highly specific, purified antibody that is derived from only one clone of cells and which recognizes a single antigen.

HYBRIDOMA TECHNOLOGY

The technology that led to the production of monoclonal antibodies and which involved the generation of an antibody-secreting B-cell line by fusing splenic-derived B cells with an immortal myeloid cell line.

ISOTYPE

The class — or type — of antibody as determined by structural features of the heavy chain constant regions. In humans there are five main isotypes: IgA (2 subclasses), IgD, IgE, IgG (4 subclasses) and IgM.

HUMANIZED ANTIBODIES

Murine monoclonal antibodies are recognized as foreign by the human immune system. To avoid this, humanized antibodies can be constructed in which rodent hypervariable regions (antigen-binding site) are grafted into a human antibody framework.

CD3

A polypeptide complex that is associated with the T-cell receptor and is involved in signal transduction. A CD3-specific monoclonal antibody blocks T-cell activation.

PEPTIDE MIMOTOPES

Peptides that mimic natural epitopes.

ANTI-IDIOTYPIC RESPONSES

The antigen-binding site of an antibody is also known as the idiotype. An antibody response to this region can generate antibodies that bear the image of the original immunogen or antigen.

PROZONE EFFECT

A decrease in an antigen–antibody reaction that occurs as the concentration of antibody or antigen increases.

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Casadevall, A., Dadachova, E. & Pirofski, La. Passive antibody therapy for infectious diseases. Nat Rev Microbiol 2, 695–703 (2004). https://doi.org/10.1038/nrmicro974

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