1887

Chapter 1 : History and Practice: Antibodies in Infectious Diseases

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Ebook: Choose a downloadable PDF or ePub file. Chapter is a downloadable PDF file. File must be downloaded within 48 hours of purchase

Buy this Chapter
Digital (?) $15.00

Preview this chapter:
Zoom in
Zoomout

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

| /docserver/preview/fulltext/10.1128/9781555817411/9781555817350_Chap01-1.gif /docserver/preview/fulltext/10.1128/9781555817411/9781555817350_Chap01-2.gif

Abstract:

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
0.6015339
Immune Systems
0.55947745
Viral Proteins
0.51189905
Infectious Diseases
0.45681798
0.6015339
Highlighted Text: Show | Hide
Loading full text...

Full text loading...

Figures

Image of Figure 1
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
Permissions and Reprints Request Permissions
Download as Powerpoint
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
Permissions and Reprints Request Permissions
Download as Powerpoint

References

/content/book/10.1128/9781555817411.chap1
1. Casadevall A,, Sharff MD . 1994. Serum therapy revisited: animal models of infection and development of passive antibody therapy. Antimicrob Agents Chemother 38 : 16951702.[PubMed] [CrossRef]
2. Casadevall A . 1996. Antibody-based therapies for emerging infectious diseases. Emerg Infect Dis 2 : 200208.[PubMed] [CrossRef]
3. Behring EA,, Kitasato S . 1890. Ueber das zustandekommen der diptherie-immunität und der tetanus-immunität bei thieren. Deutch Med Woch 49 : 11131114.
4. Klemperer G,, Klemperer F . 1891. Versuche uber immunisirung und heilung bei der pneumokokkeninfection. Berlin Klin Wochenschr 28 : 833835.
5. Flexner S,, Jobling JW . 1908. Serum treatment of epidemic cerebro-spinal meningitis. J Exp Med 10 : 141195.[CrossRef]
6. Rosington B . 2013. The drugs won’t work: top doctor warns of “apocalypse” in 20 years as bugs become resistant to antibiotics. Daily Mirror, January 24.
7. WHO . 2014. Ebola response roadmap update report. http://www.who.int/csr/resources/publications/ebola/response-roadmap/en/.
8. Chan CEZ,, Chan AHY,, Hanson BJ,, Ooi EE . 2009. The use of antibodies in the treatment of infectious diseases. Singapore Med J 50 : 663672.[PubMed]
9. Berry JD,, Gaudet RG . 2011. Antibodies in infectious diseases: polyclonals, monoclonals and niche biotechnology. New Biotechnol 28 : 489501.[PubMed] [CrossRef]
10. Cauza K,, Hinterhuber G,, Dingelmaier-Hovorka R,, Brugger K,, Klosner G,, Horvat R,, Wolff K,, Foedinger D . 2005. Expression of FcRn, the MHC class I-related receptor for IgG, in human keratinocytes. J Invest Dermatol 124 : 132139.[PubMed] [CrossRef]
11. Marasco WA,, Sui J . 2007. The growth and potential of human antiviral monoclonal antibody therapeutics. Nat Biotechnol 25 : 14211434.[PubMed] [CrossRef]
12. Wrammert J,, Koutsonanos D,, Li G-M,, Edupganti S,, Sui J,, Morrissey M,, McCausland M,, Skountzou I,, Hornig M,, Lipkin WI,, Metha A,, Razave B,, DelRio C,, Zheng N-Y,, Lee J-H,, Huang M,, All Z,, Kaur K,, Andrews S,, Amara RR,, Wang Y,, Das SR,, O’Donnel CD,, Yewdell JW,, Subbarao K,, Marasco WA,, Mulligan M,, Compans R,, Ahmed R,, Wilson PC . 2011. Broadly cross-reactive antibodies dominate the human B cell response against 2009 pandemic H1N1 influenza virus infection. J Exp Med 208 : 181193.[PubMed] [CrossRef]
13. Köhler G,, Milstein C . 1975. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256 : 495497.[PubMed] [CrossRef]
14. Casadevall A,, Dadachova E,, Pirofski LA . 2004. Passive antibody therapy for infectious diseases. Nat Rev Microbiol 2 : 695703.[PubMed] [CrossRef]
15. Triggle N . Antibiotic treatments from GPs “fail 15% of the time”. BBC News, Health, September 25.
16. Bregenholt S,, Jensen A,, Lantto J,, Hyldig S,, Haurum J . 2006. Recombinant human polyclonal antibodies: a new class of therapeutic antibodies against viral infections. Curr Pharm Des 12 : 20072015.[PubMed] [CrossRef]
17. Flego M,, Ascione A,, Cianfriglia M,, Vella S . 2013. Clinical development of monoclonal antibody-based therapy drugs in HIV and HCV diseases. BMC Med 11 : 117.[PubMed] [CrossRef]
18. de Kruif J,, Bakker ABH,, Marissen WE,, Arjen Kramer R,, Throsby M,, Rupprecht CE,, Goudsmit J . 2007. A human monoclonal antibody cocktail as a novel component of rabies post-exposure prophylaxis. Annu Rev Med 50 : 359368.[PubMed] [CrossRef]
19. Lazar GA,, Dang W,, Karki S,, Vafa O, Peng JS,, Hyun L,, Chan C,, Chung HS,, Eivazi A,, Yoder SC . 2006. Engineered antibody Fc variants with enhanced effector function. Proc Natl Acad Sci USA 103 : 40054010.[PubMed] [CrossRef]
20. Shields RL,, Namenuk AK,, Hong K,, Meng YG,, Rae J,, Briggs J,, Xie D,, Lai J,, Stadlen A,, Li B . 2001. High resolution mapping of the binding site on human IgG1 for FcγRI, FcγRII, FcγRIII, and FcRn and design of IgG1 variants with improved binding to the FcγR. J Biol Chem 276 : 65916604.[PubMed] [CrossRef]
21. Stewart R,, Thom G,, Levens M,, Güler-Gane G,, Holgate R,, Rudd PM,, Webster C,, Jermutus L,, Lund J . 2011. A variant human IgG1-Fc mediates improved ADCC. Protein Eng Des Sel 24 : 671678.[PubMed] [CrossRef]
22. Niwa R,, Hatanaka S,, Shoji-Hosaka E,, Sakurada M,, Kobayashi Y,, Uehara A,, Yokoi H,, Nakamura K,, Shitara K . 2004. Enhancement of the antibody-dependent cellular cytotoxicity of low-fucose IgG1 is independent of Fc-q gammaRIIIa functional polymorphism. Clin Cancer Res 10 : 62486255.[PubMed] [CrossRef]
23. Hezareh M,, Hessell AJ,, Jensen RC,, van de Winkel JGJ,, Parren PWHI . 2001. Effector function activities of a panel of mutants of a broadly neutralizing antibody against human immunodeficiency virus type 1. J Virol 75 : 1216112168.[PubMed] [CrossRef]
24. Hessell AJ,, Hangartner L,, Hunter M,, Havenith CD,, Beursken FJ,, Bakker JM,, Lanigan CM,, Landucci G,, Forthal DN,, Parren PW,, Marx PA,, Burton DR . 2007. Fc receptor but not complement binding is important in antibody protection against HIV. Nature 449(7158): 101104. [PubMed] [CrossRef]
25. Dall’Acqua WF,, Kiener PA,, Wu H . 2006. Properties of human IgG1s engineered for enhanced binding to the neonatal Fc receptor (FcRn). J Biol Chem 281 : 2351423524.[PubMed] [CrossRef]
26. Saylor C,, Dadachova E,, Casadevall A . 2009. Monoclonal antibody-based therapies for microbial diseases. Vaccine 275 : G38G46.[PubMed] [CrossRef]
27. Hall AE,, Domanski PJ,, Vernachio JH,, Syrbeys PJ,, Gorovits EL,, Johnson MA,, Ross JM,, Patti JM . 2003. Characterization of a protective monoclonal antibody recognizing Staphylococcus aureus MSCRAMM protein clumping factor A. Infect Immun 71 : 68646870.[PubMed] [CrossRef]
28. Bebbington C,, Yarranton G . 2008. Antibodies for the treatment of bacterial infections: current experience and future prospects. Curr Opin Biotechnol 19 : 613619.[PubMed] [CrossRef]
29. Weisman LE,, Thackray HM,, Steinhorn RH,, Walsh WF,, Lassiter HA,, Dhanireddy R,, Brozanski BS,, Palmer KG,, Trautman MS,, Escobedo M,, Meissner HC,, Sasidharan P,, Fretz J,, Kokai-Kun JF,, Mond JJ . 2011. A randomized study of a monoclonal antibody (pagibaximab) to prevent staphylococcal sepsis. Pediatrics 128 : 271279.[PubMed] [CrossRef]
30. Weintraub JA,, Hilton JF,, White JM,, Hoover CI,, Wycoff KL,, Yu L,, Larrick JW,, Featherstone JD . 2005. Clinical trial of a plant-derived antibody on recolonization of mutans streptococci. Caries Res 19 : 241250.[PubMed] [CrossRef]
31. Baer M,, Sawa T,, Flynn P . 2009. An engineered human antibody Fab fragment specific for Pseudomonas aeruginosa PcrV antigen has potent anti-bacterial activity. Infect Immun 77 : 10831090.[PubMed] [CrossRef]
32. Secher T,, Fauconnier L,, Szade A . 2011. Anti-pseudomonas aeruginosa serotype 011 LPS immunoglobulin M monoclonal antibody panobacumab (KBPA101) confers protection in a murine model of acute lung infection. J Antimicrob Chemother 66 : 11001109.[PubMed] [CrossRef]
33. Migone T,, Subramanian GM,, Bolmer SD . 2009. Raxibacumab for the treatment of inhalational anthrax. N Engl J Med 361 : 135144.[PubMed] [CrossRef]
34. Lowy I,, Molrine DC,, Leav BA . 2010. Treatment with monoclonal antibodies against Clostridium\ difficile toxins. N Engl J Med 362 : 197205.[PubMed] [CrossRef]
35. Ter Meulen J . 2011. Monoclonal antibodies in infectious diseases: clinical pipeline in 2011. Infect Dis Clin N Am 25 : 798802.[PubMed] [CrossRef]
36. Broering TJ,, Garrity KA,, Boatright NK . 2009. Identification and characterization of broadly neutralizing human monoclonal antibodies directed against the E2 envelope glycoprotein of hepatitis C virus. J Virol 83 : 1247312482.[PubMed] [CrossRef]
37. Soares MM,, King SW,, Thorpe PE . 2008. Targeting inside-out phosphatidylserine as a therapeutic strategy for viral diseases. Nat Med 14 : 13571362.[PubMed] [CrossRef]
38. Bruno BJ,, Jacobson JM . 2010. Ibalizumab: an anti-CD4 monoclonal antibody for the treatment of HIV-1 infection. J Antimicrob Chemother 65 : 18391841.[PubMed] [CrossRef]
39. Li L,, Sun T,, Yang K . 2010. Monoclonal CCR5 antibody for treatment of people with HIV infection (review). Cochrane Database Syst Rev 8 : CD008439. [PubMed] [CrossRef]
40. Quiambao B,, Bakker A,, Bermal NN . 2009. Evaluation of the safety and neutralizing activity of CL184, a monoclonal antibody cocktail against rabies, in a phase II study in healthy adolescents and children. Quebec, Canada: Presentation at RITA XX, Rabies in the Americas.
41. Larsen RA,, Pappas PG,, Perfect J,, Aberg JA,, Casadevall A,, Cloud GA . 2005. Phase I evaluation of the safety and pharmacokinetics of murine-derived anticryptococcal antibody 18b7 in subjects with treated cryptococcal meningitis. Antimicrob Agents Chemother 49 : 952958.[PubMed] [CrossRef]

Tables

Generic image for table
TABLE 1

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
Generic image for table
TABLE 2

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

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error