Chapter 1 : History and Practice: Antibodies in Infectious Diseases

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History and Practice: Antibodies in Infectious Diseases, Page 1 of 2

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aims to inform, update, and inspire students, teachers, researchers, pharmaceutical developers, and health care professionals on the status of the development of antibody-based therapies for treating infectious diseases and the potential for these in times of growing antibiotic resistance to provide alternative treatment solutions to the currently used antibiotics and new treatments for infectious diseases where no proper treatments are available.

Citation: Hey A. 2015. History and Practice: Antibodies in Infectious Diseases, p 3-21. In Crowe J, Boraschi D, Rappuoli R (ed), Antibodies for Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.AID-0026-2014

Key Concept Ranking

Complement System
Immune Systems
Viral Proteins
Infectious Diseases
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Figure 1

(Left panel) Model of antibody structure exemplified by IgG. On top the antigen-binding sites in orange each contain one variable light and variable heavy domain with the three complementarity determining regions (CDRs) that are responsible for the specific binding of the antibody to its target. For each arm of the antibody, an additional set of variable heavy and light domains, together with the CDR-containing domains, represent the two fragment antigen binding (Fab) regions. The two Fabs are held together via two disulfide bridges. Below the Fabs is the Fc region, which contains four constant heavy domains. On the upper pair of these domains are binding sites for oligosaccharides, which have major importance for the ability of the antibody Fc part to trigger effector functions when the Fc portion is bound to Fc gamma receptors on natural killer cells, neutrophil granulocytes, monocytes/macrophages, dendritic cells, and B cells. (Right panel) Examples of some of the antibody-derived alternative formats used to exploit the specific features of the CDRs, the Fabs, and the Fc parts of the antibodies. ScFv: The single chain fragment variable consists of the variable domains of the heavy and light chains held together by a flexible linker. This can also be used as a carrier of a cytotoxic drug in a so-called antibody drug complex (ADC) where the specificity of the ScFv is used to target the cytotoxic drug to, e.g., a tumor. Bite (bi-specific T cell engager): Fusion proteins consisting of two ScFvs, one directed against the target on a tumor cell and the other against the T cell receptor (CD3). Diabody: ScFv dimers where short linker peptides (five amino acids) ensure dimerization, and not folding, of the ScFvs. Fab and F(ab) fragments: Single Fab fragments or fragments containing two Fabs linked via disulfide bridges. This is used where effector functions related to the Fc part of the antibody are unwanted and where a smaller size is desired to obtain better tissue penetration in, e.g., tumors. Due to the lack of the FcRn binding via the Fc part, Fab and F(ab) fragments have much shorter half-lives (hours or days) than full-size antibodies (weeks). These can also be used as carriers of cytotoxic payloads or cytotoxic radioactive isotopes and for the F(ab) fragments can be constructed as bi-specifics which can cross-link immune cells and target cells. Fc fusion protein: Fusion protein containing the Fc domain of an immunoglobulin bound to a peptide. The peptide can be a ligand for a specific receptor on a target cell or a blocking peptide for a soluble ligand. The Fc part provides a longer half-life to the construct and the potential to bind to and engage effector functions in the killing of, e.g., tumor cells or infected cells. ADCs/RIAs and bi-specifics: Full-size IgG antibodies carrying either a cytotoxic chemical or radioactive payload, which may also carry different CDRs, enabling cross-linking of effector and target cells for increased killing. doi:10.1128/microbiolspec.AID-0026-2014.f1

Citation: Hey A. 2015. History and Practice: Antibodies in Infectious Diseases, p 3-21. In Crowe J, Boraschi D, Rappuoli R (ed), Antibodies for Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.AID-0026-2014
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Image of Figure 2
Figure 2

Effector functions of antibodies. (a) Antibodies bind to pathogen-derived or endogenous antigens expressed on the surface of an infected cell, which triggers binding to Fc receptors on natural killer cells and lysis of the infected cell by antibody-dependent cellular cytotoxicity. (b) Antibodies bind to pathogen-derived or endogenous antigens expressed on the surface of infected cells, which triggers activation of complement through binding of complement factor C1q. (c) Neutralization. Top: Bacterial toxin neutralized by bound antigen. Bottom: Antibody bound to either receptor for the virus or to the virus itself, which blocks virus binding and entry into the cell. (d) Antibody bound to viral surface proteins binds to Fc receptors on phagocytic cells, e.g., macrophages, and triggers endocytosis and destruction of virus in endolysosome. doi:10.1128/microbiolspec.AID-0026-2014.f2

Citation: Hey A. 2015. History and Practice: Antibodies in Infectious Diseases, p 3-21. In Crowe J, Boraschi D, Rappuoli R (ed), Antibodies for Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.AID-0026-2014
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Approved and pending antibody-based therapies

Citation: Hey A. 2015. History and Practice: Antibodies in Infectious Diseases, p 3-21. In Crowe J, Boraschi D, Rappuoli R (ed), Antibodies for Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.AID-0026-2014
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Pros and cons of antibody based therapies related to serum therapy and antibiotics

Citation: Hey A. 2015. History and Practice: Antibodies in Infectious Diseases, p 3-21. In Crowe J, Boraschi D, Rappuoli R (ed), Antibodies for Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.AID-0026-2014

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