Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Current Allergy and Asthma Reports
Published in: Current Allergy and Asthma Reports 2/2016

Open Access 01-02-2016 | Immunotherapy and Immunomodulators (B Vickery, Section Editor)

The Cloning and Expression of Human Monoclonal Antibodies: Implications for Allergen Immunotherapy

Author: Louisa K. James

Published in: Current Allergy and Asthma Reports | Issue 2/2016

Login to get access

Abstract

Allergic responses are dependent on the highly specific effector functions of IgE antibodies. Conversely, antibodies that block the activity of IgE can mediate tolerance to allergen. Technologies that harness the unparalleled specificity of antibody responses have revolutionized the way that we diagnose and treat human disease. This area of research continues to advance at a rapid pace and has had a significant impact on our understanding of allergic disease. This review will present an overview of humoral responses and provide an up-to-date summary of technologies used in the generation of human monoclonal antibodies. The impact that monoclonal antibodies have on allergic disease will be discussed, with a particular focus on allergen immunotherapy, which remains the only form of treatment that can modulate the underlying immune mechanisms and induce long-term clinical tolerance.
Literature
1.
2.
Freeman J. Further observations on the treatment of hay fever by hypodermic inoculations of pollen vaccine. Lancet. 1911;2:814–7.CrossRef
3.
Calderón MA, Rodríguez Del Río P, Vidal C, Just J, Pfaar O, Linneberg A, et al. An EAACI "european survey on adverse systemic reactions in allergen immunotherapy (EASSI)": the methodology. Clin Transl Allergy. 2014;21:22.CrossRef
4.
Brieva JA, Roldán E, De la Sen ML, Rodriguez C. Human in vivo-induced spontaneous IgG-secreting cells from tonsil, blood and bone marrow exhibit different phenotype and functional level of maturation. Immunology. 1991;72:580–3.PubMedCentralPubMed
5.
6.
Boes M. Role of natural and immune IgM antibodies in immune responses. Mol Immunol. 2000;37:1141–9.CrossRefPubMed
7.
Chen K, Xu W, Wilson M, He B, Miller NW, Bengtén E, et al. Immunoglobulin D enhances immune surveillance by activating antimicrobial, proinflammatory and B cell-stimulating programs in basophils. Nat Immunol. 2009;10:889–98.PubMedCentralCrossRefPubMed
8.
9.•
Vidarsson G, Dekkers G, Rispens T. IgG subclasses and allotypes: from structure to effector functions. Front Immunol. 2014;5:520. An up to date review of the IgG subclasses.PubMedCentralCrossRefPubMed
10.
Barrett DJ, Ayoub EM. IgG2 subclass restriction of antibody to pneumococcal polysaccharides. Clin Exp Immunol. 1986;63:127–34.PubMedCentralPubMed
11.
Aalberse RC, Stapel SO, Schuurman J, Rispens T. Immunoglobulin G4: an odd antibody. Clin Exp Allergy. 2009;39:469–77.CrossRefPubMed
12.•
13.
Deshpande V, Zen Y, Chan JK, Yi EE, Sato Y, Yoshino T, et al. Consensus statement on the pathology of IgG4-related disease. Mod Pathol. 2012;25:1181–92.CrossRefPubMed
14.
15.
16.
Köhler G, Milstein C. Continuous cultures of fused cells secreting anti-body of predefined specificity. Nature. 1975;256:495.CrossRefPubMed
17.
Miller RA, Oseroff AR, Stratte PT, Levy R. Blood. 1983;5:988–95.
18.
Morrison SL, Johnson MJ, Herzenberg LA, Oi VT. Chimeric human antibody molecules: mouse antigen-binding domains with human constant region domains. Proc Natl Acad Sci U S A. 1984;81:6851–5.PubMedCentralCrossRefPubMed
19.
Boulianne GL, Hozumi N, Shulman MJ. Production of functional chimaeric mouse/human antibody. Nature. 1984;312:643–6.CrossRefPubMed
20.
Jones PT, Dear PH, Foote J, Neuberger MS, Winter G. Replacing the complementarity-determining regions in a human antibody with those from a mouse. Nature. 1986;321:522–5.CrossRefPubMed
21.
Todd PA, Brogden RN. Muromonab CD3. A review of its pharmacology and therapeutic potential. Drugs. 1989;37:871–99.CrossRefPubMed
22.
Alt FW, Keith Blackwell T, Yancopoulos GD. Immunoglobulin genes in transgenic mice. Trends Genet. 1985;1:231–6.CrossRef
23.
Green LL, Hardy MC, Maynard-Currie CE, Tsuda H, Louie DM, Mendez MJ, et al. Antigen-specific human monoclonal antibodies from mice engineered with human Ig heavy and light chain YACs. Nat Genet. 1994;7:13–21.CrossRefPubMed
24.
Lonberg N, Taylor LD, Harding FA, Trounstine M, Higgins KM, Schramm SR, et al. Antigen-specific human antibodies from mice comprising four distinct genetic modifications. Nature. 1994;368:856–9.CrossRefPubMed
25.
Smith GP. Filamentous fusion phage: novel expression vectors that display cloned antigens on the virion surface. Science. 1985;228:1315–7.CrossRefPubMed
26.
McCafferty J, Griffiths AD, Winter G, Chiswell DJ. Phage antibodies: filamentous phage displaying antibody variable domains. Nature. 1990;348:552–4.CrossRefPubMed
27.
Lee CM, Iorno N, Sierro F, Christ D. Selection of human antibody fragments by phage display. Nat Protoc. 2007;2:3001–8.CrossRefPubMed
28.
Kozbor D, Roder JC. Requirements for the establishment of high-tittered human monoclonal antibodies against tetanus toxoid using the Epstein-Barr virus technique. J Immunol. 1981;127:1275–80.PubMed
29.
Traggiai E, Becker S, Subbarao K, Kolesnikova L, Uematsu Y, Gismondo MR, et al. An efficient method to make human monoclonal antibodies from memory B cells: potent neutralization of SARS coronavirus. Nat Med. 2004;10:871–5.CrossRefPubMed
30.
Tiller T, Meffre E, Yurasov S, Tsuiji M, Nussenzweig MC, Wardemann H. Efficient generation of monoclonal antibodies from single human B cells by single cell RT-PCR and expression vector cloning. J Immunol Methods. 2008;329:112–24.PubMedCentralCrossRefPubMed
31.
Wrammert J, Smith K, Miller J, Langley WA, Kokko K, Larsen C, et al. Rapid cloning of high-affinity human monoclonal antibodies against influenza virus. Nature. 2008;453:667–71.PubMedCentralCrossRefPubMed
32.
Di Niro R, Mesin L, Raki M, Zheng NY, Lund-Johansen F, Lundin KE, et al. Rapid generation of rotavirus-specific human monoclonal antibodies from small-intestinal mucosa. J Immunol. 2010;185:5377–83.CrossRefPubMed
33.
Wu X, Yang ZY, Li Y, Hogerkorp CM, Schief WR, Seaman MS, et al. Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1. Science. 2010;329:856–61.PubMedCentralCrossRefPubMed
34.
Maskus DJ, Bethke S, Seidel M, Kapelski S, Addai-Mensah O, Boes A, et al. Isolation, production and characterization of fully human monoclonal antibodies directed to Plasmodium falciparum MSP10. Malar J. 2015;14:276.PubMedCentralCrossRefPubMed
35.••
Patil SU, Ogunniyi AO, Calatroni A, Tadigotla VR, Ruiter B, Ma A, et al. Peanut oral immunotherapy transiently expands circulating Ara h 2-specific B cells with a homologous repertoire in unrelated subjects. J Allergy Clin Immunol. 2015;136:125–34. In this study the authors used fluorescently-labeled antigen to isolate, clone and express a number of peanut-specific antibodies from peripheral blood.CrossRefPubMed
36.
James LK, Bowen H, Calvert RA, Dodev TS, Shamji MH, Beavil AJ, et al. Allergen specificity of IgG(4)-expressing B cells in patients with grass pollen allergy undergoing immunotherapy. J Allergy Clin Immunol. 2012;130:663–70.CrossRefPubMed
37.
Huang J, Doria-Rose NA, Longo NS, Laub L, Lin CL, Turk E, et al. Isolation of human monoclonal antibodies from peripheral blood B cells. Nat Protoc. 2013;8:1907–15.CrossRefPubMed
38.
39.
Wu YC, James LK, Vander Heiden JA, Uduman M, Durham SR, Kleinstein SH, et al. Influence of seasonal exposure to grass pollen on local and peripheral blood IgE repertoires in patients with allergic rhinitis. J Allergy Clin Immunol. 2014;134:604–12.PubMedCentralCrossRefPubMed
40.
Reddy ST, Ge X, Miklos AE, Hughes RA, Kang SH, Hoi KH, et al. Monoclonal antibodies isolated without screening by analyzing the variable-gene repertoire of plasma cells. Nat Biotechnol. 2010;28:965–9.CrossRefPubMed
41.••
DeKosky BJ, Ippolito GC, Deschner RP, Lavinder JJ, Wine Y, Rawlings BM, et al. High-throughput sequencing of the paired human immunoglobulin heavy and light chain repertoire. Nat Biotechnol. 2013;31:166–9. In this study emulsion PCR was used to amplify naturally paired heavy and light chain sequences of single peripheral B cells prior to high-throughput sequencing.PubMedCentralCrossRefPubMed
42.••
Tan YC, Kongpachith S, Blum LK, Ju CH, Lahey LJ, Lu DR, et al. Barcode-enabled sequencing of plasmablast antibody repertoires in rheumatoid arthritis. Arthritis Rheum. 2014;66:2706–15. Using a novel DNA-barcoding method, the authors sequenced paired antibody repertoires from peripheral blood plasmablasts of rheumatoid arthritis patients. Based on these sequences, recombinant monoclonal antibodies were generated by molecular cloning and shown to bind to autoantigens implicated in disease pathogenesis.CrossRef
43.•
Lu DR, Tan YC, Kongpachith S, Cai X, Stein EA, Lindstrom TM, et al. Identifying functional anti-Staphylococcus aureus antibodies by sequencing antibody repertoires of patient plasmablasts. Clin Immunol. 2014;152:77–89. In a validation of the DNA-barcoding approach described above, the authors isolated, cloned and characterized the functional activity of human Staphylococcus aureus-specific antibodies.PubMedCentralCrossRefPubMed
44.
45.
Senti G, von Moos S, Tay F, Graf N, Johansen P, Kündig TM. Determinants of efficacy and safety in epicutaneous allergen immunotherapy: summary of three clinical trials. Allergy. 2015;70:707–10.PubMedCentralCrossRefPubMed
46.
47.
Jutel M, Agache I, Bonini S, Burks AW, Calderon M, Canonica W, et al. International consensus on allergy immunotherapy. J Allergy Clin Immunol. 2015;136:556–68.CrossRefPubMed
48.
49.
Presta LG, Lahr SJ, Shields RL, Porter JP, Gorman CM, Fendly BM, et al. Humanization of an antibody directed against IgE. J Immunol. 1993;151:2623–32.PubMed
50.
Holgate ST, Djukanović R, Casale T, Bousquet J. Anti-immunoglobulin E treatment with omalizumab in allergic diseases: an update on anti-inflammatory activity and clinical efficacy. Clin Exp Allergy. 2005;35:408–16.CrossRefPubMed
51.
52.
Massanari M, Nelson H, Casale T, Busse W, Kianifard F, Geba GP, et al. Effect of pretreatment with omalizumab on the tolerability of specific immunotherapy in allergic asthma. J Allergy Clin Immunol. 2010;125:383–9.CrossRefPubMed
53.
Casale TB, Busse WW, Kline JN, Ballas ZK, Moss MH, Townley RG, et al. Omalizumab pretreatment decreases acute reactions after rush immunotherapy for ragweed-induced seasonal allergic rhinitis. J Allergy Clin Immunol. 2006;117:134–40.CrossRefPubMed
54.
Kuehr J, Brauburger J, Zielen S, Schauer U, Kamin W, Von Berg A, et al. Efficacy of combination treatment with anti-IgE plus specific immunotherapy in polysensitized children and adolescents with seasonal allergic rhinitis. J Allergy Clin Immunol. 2002;109:274–80.CrossRefPubMed
55.
Rolinck-Werninghaus C, Hamelmann E, Keil T, Kulig M, Koetz K, Gerstner B, et al. The co-seasonal application of anti-IgE after preseasonal specific immunotherapy decreases ocular and nasal symptom scores and rescue medication use in grass pollen allergic children. Allergy. 2004;59:973–9.CrossRefPubMed
56.
Kamin W, Kopp MV, Erdnuess F, Schauer U, Zielen S, Wahn U. Safety of anti-IgE treatment with omalizumab in children with seasonal allergic rhinitis undergoing specific immunotherapy simultaneously. Pediatr Allergy Immunol. 2010;21:160–5.CrossRef
57.
Nadeau K, Schneider L, Hoyte E, Borras I, Umetsu D. Rapid oral desensitization in combination with omalizumab therapy in patients with cow’s milk allergy. J Allergy Clin Immunol. 2011;127:1722–4.
58.••
Schneider LC, Rachid R, LeBovidge J, Blood E, Mittal M, Umetsu DT. A pilot study of omalizumab to facilitate rapid oral desensitization in high-risk peanut-allergic patients. J Allergy Clin Immunol. 2013;132:1368–74. Omalizumab was administered prior to and during oral peanut desensitization in children at high risk of severe allergic reactions. This pilot study provided evidence that omalizumab can facilitate oral immunotherapy for food allergy by reducing side effects in high risk patients.PubMedCentralCrossRefPubMed
59.•
Cohen ES, Dobson CL, Käck H, Wang B, Sims DA, Lloyd CO, et al. A novel IgE-neutralizing antibody for the treatment of severe uncontrolled asthma. MAbs. 2014;6:756–64. Using phage-display technology and antibody engineering, the authors describe a monoclonal anti-IgE with improved affinity binding to IgE.CrossRefPubMed
60.
Hilvering B, Pavord ID. What goes up must come down: biomarkers and novel biologicals in severe asthma. Clin Exp Allergy. 2015;45:1162–9.CrossRefPubMed
61.
Chaker AM, Shamji MH, Dumitru FA, Calderon MA, Scadding GW, Makatsori M, et al. Short-term subcutaneous grass pollen immunotherapy under the umbrella of anti-IL-4: a randomized controlled trial. J Allergy Clin Immunol. 2015.
62.
Cooke RA, Loveless M, Stull A. Studies on immunity in a type of human allergy (hayfever): serological response of non-sensitive individuals to pollen injections. J Exp Med. 1937;66:689–96.PubMedCentralCrossRefPubMed
63.
Lessof MH, Sobokta AK, Lichtenstein LM. Effects of passive antibody in bee venom anaphylaxis. Johns Hopkins Med J. 1978;142:1–7.PubMed
64.
Bousquet J, Fontez A, Aznar R, Robinet-Levy M, Michel FB. Combination of passive and active immunization in honeybee venom immunotherapy. J Allergy Clin Immunol. 1987;79:947–54.CrossRefPubMed
65.
Muller UR, Morris T, Bischof M, Friedli H, Skarvil F. Combined active and passive immunotherapy in honeybee-sting allergy. J Allergy Clin Immunol. 1986;78:115–22.CrossRefPubMed
66.
Flicker S, Gadermaier E, Madritsch C, Valenta R. Passive immunization with allergen-specific antibodies. Curr Top Microbiol Immunol. 2011;352:141–59.PubMed
67.
68.
Moerch U, Haahr Hansen M, Vest Hansen NJ, Rasmussen LK, Oleksiewicz MB, Frandsen TP, et al. Allergen-specific polyclonal antibodies reduce allergic disease in a mouse model of allergic asthma. Int Arch Allergy Immunol. 2006;140:261–9.CrossRefPubMed
69.••
Zuidmeer-Jongejan L, Fernandez-Rivas M, Poulsen LK, Neubauer A, Asturias J, Blom L, et al. FAST: towards safe and effective subcutaneous immunotherapy of persistent life-threatening food allergies. Clin Transl Allergy. 2012;2:5. A review of the FAST (food allergy specific immunotherapy) project which aims to develop safer hypoallergenic recombinant allergens for allergen immunotherapy. The study will evaluate and compare methods for the production of hypoallergens, namely chemical modification versus site-directed mutagenesis.PubMedCentralCrossRefPubMed
70.
Zuidmeer-Jongejan L, Huber H, Swoboda I, Rigby N, Versteeg SA, Jensen BM, et al. Development of a hypoallergenic recombinant parvalbumin for first-in-man subcutaneous immunotherapy of fish allergy. Int Arch Allergy Immunol. 2015;166:41–51.CrossRefPubMed
71.
Shreffler WG, Beyer K, Chu TH, Burks AW, Sampson HA. Microarray immunoassay: association of clinical history, in vitro IgE function, and heterogeneity of allergenic peanut epitopes. J Allergy Clin Immunol. 2004;113:776–82.CrossRefPubMed
72.
73.
Padlan EA, Silverton EW, Sheriff S, Cohen GH, Smith-Gill SJ, Davies DR. Structure of an antibody-antigen complex: crystal structure of the HyHEL-10 Fab-lysozyme complex. Proc Natl Acad Sci U S A. 1989;86:5938–42.PubMedCentralCrossRefPubMed
74.
Mirza O, Henriksen A, Ipsen H, Larsen JN, Wissenbach M, Spangfort MD, et al. Dominant epitopes and allergic cross-reactivity: complex formation between a Fab fragment of a monoclonal murine IgG antibody and the major allergen from birch pollen Bet v 1. J Immunol. 2000;165:331–8.CrossRefPubMed
75.
Niemi M, Jylhä S, Laukkanen ML, Söderlund H, Mäkinen-Kiljunen S, Kallio JM, et al. Molecular interactions between a recombinant IgE antibody and the beta-lactoglobulin allergen. Structure. 2007;15:1413–21.CrossRefPubMed
76.
Padavattan S, Schirmer T, Schmidt M, Akdis C, Valenta R, Mittermann I, et al. Identification of a B-cell epitope of hyaluronidase, a major bee venom allergen, from its crystal structure in complex with a specific Fab. J Mol Biol. 2007;368:742–52.CrossRefPubMed
77.
Li M, Gustchina A, Alexandratos J, Wlodawer A, Wünschmann S, Kepley CL, et al. Crystal structure of a dimerized cockroach allergen Bla g 2 complexed with a monoclonal antibody. J Biol Chem. 2008;283:22806–14.PubMedCentralCrossRefPubMed
78.
Padavattan S, Flicker S, Schirmer T, Madritsch C, Randow S, Reese G, et al. High-affinity IgE recognition of a conformational epitope of the major respiratory allergen Phl p 2 as revealed by X-ray crystallography. J Immunol. 2009;182:2141–51.CrossRefPubMed
79.
Chruszcz M, Pomés A, Glesner J, Vailes LD, Osinski T, Porebski PJ, et al. Molecular determinants for antibody binding on group 1 house dust mite allergens. J Biol Chem. 2012;287:7388–98.PubMedCentralCrossRefPubMed
80.
Spangfort MD, Mirza O, Ipsen H, Van Neerven RJ, Gajhede M, Larsen JN. Dominating IgE-binding epitope of Bet v 1, the major allergen of birch pollen, characterized by X-ray crystallography and site-directed mutagenesis. J Immunol. 2003;171:3084–90.CrossRefPubMed
81.
Holliger P, Hudson PJ. Engineered antibody fragments and the rise of single domains. Nat Biotechnol. 2005;23:1126–36.CrossRefPubMed
82.
83.
Chowdhury PS, Pastan I. Improving antibody affinity by mimicking somatic hypermutation in vitro. Nat Biotechnol. 1999;17:568–72.CrossRefPubMed
Metadata
Title
The Cloning and Expression of Human Monoclonal Antibodies: Implications for Allergen Immunotherapy
Author
Louisa K. James
Publication date
01-02-2016
Publisher
Springer US
Published in
Current Allergy and Asthma Reports / Issue 2/2016
Print ISSN: 1529-7322
Electronic ISSN: 1534-6315
DOI
https://doi.org/10.1007/s11882-015-0588-z

Other articles of this Issue 2/2016

Current Allergy and Asthma Reports 2/2016 Go to the issue

Rhinitis (JJ Oppenheimer and J Corren, Section Editors)

Adherence to Sublingual Immunotherapy

Rhinitis (JJ Oppenheimer and J Corren, Section Editors)

Understanding Biofilms in Chronic Sinusitis

Allergens (RK Bush and JA Woodfolk, Section Editors)

T Cell Epitope Peptide Therapy for Allergic Diseases

Immune Deficiency and Dysregulation (DP Houston and C Kuo, Section Editors)

Immune-Microbiota Interactions: Dysbiosis as a Global Health Issue

Allergens (RK Bush and JA Woodfolk, Section Editors)

The Immunologic Mechanisms of Eosinophilic Esophagitis

Rhinosinusitis (J Mullol, Section Editor)

Risk Factors and Comorbidities in Chronic Rhinosinusitis