261:
252:(APCs), such as a B cell or Dendritic Cell, will present these substances as peptides, which T cells may recognize. This may result in unwanted immunogenicity, including ADAs and autoimmune diseases, such as autoimmune thrombocytopenia (ITP) following exposure to recombinant thrombopoietin and pure red cell aplasia, which was associated with a particular formulation of erythropoietin (Eprex).
315:, by exchanging the murine constant and complementary regions of the immunoglobulin chains with the human counterparts. Although this has reduced the sometimes extreme immunogenicity associated with murine mAbs, the anticipation that all fully human mAbs would have not possess unwanted immunogenic properties remains unfulfilled.
336:
One approach is to parse protein sequences into overlapping nonamer (that is, 9 amino acid) peptide frames, each of which is then evaluated for binding potential to each of six common class I HLA alleles that “cover” the genetic backgrounds of most humans worldwide. By calculating the density of
65:
A challenge in biotherapy is predicting the immunogenic potential of novel protein therapeutics. For example, immunogenicity data from high-income countries are not always transferable to low-income and middle-income countries. Another challenge is considering how the immunogenicity of vaccines
280:. Consequently, the high immunogenicity limited efficacy and was associated with severe infusion reactions. Although the exact mechanism is unclear, it is suspected that the mAbs are inducing infusion reactions by eliciting antibody antigen interactions, such as increased formation of
332:
tools. Immunoinformatics algorithms for identifying T-cell epitopes are now being applied to triage protein therapeutics into higher risk and low risk categories. These categories refer to assessing and analyzing whether an immunotherapy or vaccine will cause unwanted immunogenicity.
337:
high-scoring frames within a protein, it is possible to estimate a protein's overall “immunogenicity score”. In addition, sub-regions of densely packed high scoring frames or “clusters” of potential immunogenicity can be identified, and cluster scores can be calculated and compiled.
611:
Samson, Sandrine I.; Leventhal, Phillip S.; Salamand, Camille; Meng, Ya; Seet, Bruce T.; Landolfi, Victoria; Greenberg, David; Hollingsworth, Rosalind (4 March 2019). "Immunogenicity of high-dose trivalent inactivated influenza vaccine: a systematic review and meta-analysis".
340:
Using this approach, the clinical immunogenicity of a novel protein therapeutics can be calculated. Consequently, a number of biotech companies have integrated in silico immunogenicity into their pre-clinical process as they develop new protein drugs.
104:). Antigenicity was more commonly used in the past to refer to what is now known as immunogenicity, and the two terms are still often used interchangeably. However, strictly speaking, immunogenicity refers to the ability of an antigen to induce an
1022:
Stryjewska, Agnieszka; Kiepura, Katarzyna; Librowski, Tadeusz; Lochyński, Stanisław (September 2013). "Biotechnology and genetic engineering in the new drug development. Part II. Monoclonal antibodies, modern vaccines and gene therapy".
56:
Unwanted immunogenicity is an immune response by an organism against a therapeutic antigen. This reaction leads to production of anti-drug-antibodies (ADAs), inactivating the therapeutic effects of the treatment and potentially inducing
1093:
Pecoraro, Valentina; De Santis, Elena; Melegari, Alessandra; Trenti, Tommaso (June 2017). "The impact of immunogenicity of TNFα inhibitors in autoimmune inflammatory disease. A systematic review and meta-analysis".
108:. Thus an antigen might bind specifically to a T or B cell receptor, but not induce an adaptive immune response. If the antigen does induce a response, it is an 'immunogenic antigen', which is referred to as an
233:. Likewise, T Cell epitopes can cause unwanted immunogenicity, including the development of ADAs. A key determinant in T cell epitope immunogenicity is the binding strength of T cell epitopes to
562:
Nic
Lochlainn, Laura M; de Gier, Brechje; van der Maas, Nicoline; Strebel, Peter M; Goodman, Tracey; van Binnendijk, Rob S; de Melker, Hester E; Hahné, Susan J M (November 2019).
879:
Singh, Surjit; Kumar, Nitish K.; Dwiwedi, Pradeep; Charan, Jaykaran; Kaur, Rimplejeet; Sidhu, Preeti; Chugh, Vinay K. (9 October 2018). "Monoclonal
Antibodies: A Review".
503:
1294:
Porcelli, Steven A.; Modlin, Robert L. (April 1999). "THE CD1 SYSTEM: Antigen-Presenting
Molecules for T Cell Recognition of Lipids and Glycolipids".
328:
T cell epitope content, which is one of the factors that contributes to the risk of immunogenicity can now be measured relatively accurately using
809:
664:
1265:
De Groot, Anne S.; Martin, William (May 2009). "Reducing risk, improving outcomes: Bioengineering less immunogenic protein therapeutics".
564:"Immunogenicity, effectiveness, and safety of measles vaccination in infants younger than 9 months: a systematic review and meta-analysis"
1336:
260:
1202:
241:) molecules. Epitopes with higher binding affinities are more likely to be displayed on the surface of a cell. Because a T cell's
831:
234:
214:
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recognizes a specific epitope, only certain T cells are able to respond to a certain peptide bound to MHC on a cell surface.
830:
Weber, Constanze A.; Mehta, Preema J.; Ardito, Matt; Moise, Lenny; Martin, Bill; De Groot, Anne S. (30 September 2009).
790:"The Acquired Immune System Response to Biomaterials, Including Both Naturally Occurring and Synthetic Biomaterials"
329:
248:
When protein drug therapeutics, (as in enzymes, monoclonals, replacement proteins) or vaccines are administered,
67:
136:
such as a protein or polysaccharide to increase immunogenic potency so that they can evoke an immune response.
105:
249:
238:
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and few polysaccharides have immunogenic properties, which allows them to induce humoral immune responses.
53:, protecting the organism from future exposure. Immunogenicity is a central aspect of vaccine development.
504:"The efficacy, effectiveness, and immunogenicity of influenza vaccines in Africa: a systematic review"
128:
are relatively small molecules and/or have non-immunogenic properties. Consequently, they may require
688:
Dowds, C. Marie; Kornell, Sabin-Christin; Blumberg, Richard S.; Zeissig, Sebastian (1 January 2014).
277:
178: :- Molecules having bigger size, particularly those greater than10kDa, will be more immunogenic
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1131:"Immunogenicity of Biotherapeutics: Causes and Association with Posttranslational Modifications"
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De Groot, Anne S.; Scott, David W. (November 2007). "Immunogenicity of protein therapeutics".
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Lindsey, Benjamin B; Armitage, Edwin P; Kampmann, Beate; de Silva, Thushan I (April 2019).
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Baker, Matthew; Reynolds, Helen M.; Lumicisi, Brooke; Bryson, Christine J. (October 2010).
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101:
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49:, where the injection of an antigen (the vaccine) provokes an immune response against the
38:
70:, immunogenicity should be investigated in a target population since animal testing and
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1210:
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Lonberg, Nils; Huszar, Dennis (January 1995). "Human
Antibodies from Transgenic Mice".
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739:"The Modulation of Adaptive Immune Responses by Bacterial Zwitterionic Polysaccharides"
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Leroux-Roels, Geert; Bonanni, Paolo; Tantawichien, Terapong; Zepp, Fred (August 2011).
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455:"Immunogenicity of protein therapeutics: The key causes, consequences and challenges"
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Immunogenicity is influenced by multiple characteristics of an antigen:
832:"T cell epitope: Friend or Foe? Immunogenicity of biologics in context"
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in the body of a human or other animal. It may be wanted or unwanted:
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292:, causing allergy-like symptoms as well as the release of additional
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85:
973:"Immunogenicity of Innovative and Biosimilar Monoclonal Antibodies"
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Stephen, Tom Li; Groneck, Laura; Kalka-Moll, Wiltrud Maria (2010).
259:
121:
88:) to bind specifically with a group of certain products that have
788:
Fishman, Jonathan M.; Wiles, Katherine; Wood, Kathryn J. (2015).
303:
has resulted in the decrease in immunogenicity, (also known as
307:), of mAbs. Genetic engineering has led to the generation of
27:
Ability of a foreign substance to provoke an immune response
1129:
Kuriakose, Anshu; Chirmule, Narendra; Nair, Pradip (2016).
74:
models cannot precisely predict immune response in humans.
229:
epitope content is one of the factors that contributes to
213:
Degradability (ability to be processed & presented as
264:
1252:
1195:
Immunobiology. The Immune System in Health and
Disease.
971:
Doevendans, Erik; Schellekens, Huub (5 March 2019).
80:is the capacity of a chemical structure (either an
1324:
657:WHO Expert Committee on Biological Standardization
146:Proteins and some lipids/glycolypids can serve as
33:is the ability of a foreign substance, such as an
153:Proteins are significantly more immunogenic than
272:(mAbs) are used for several diseases, including
825:
823:
821:
1193:, Paul Travers, Mark Walport, Mark Shlomchik:
66:changes with age. Therefore, as stated by the
1197:6th Edition. Garland Science, New York 2004,
8:
922:Schnyder, Benno; Pichler, Werner J. (2009).
1323:Cruse, Julius M.; Lewis, Robert E. (1998).
45:Wanted immunogenicity typically relates to
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1211:"Immunotoxicity of monoclonal antibodies"
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284:(IgE) antibodies, which may bind onto
187:Chemical composition and heterogeneity
1251:The European Immunogenicity Platform
1187:Immunologists' Toolbox: Immunization.
743:International Journal of Microbiology
7:
924:"Mechanisms of Drug-Induced Allergy"
796:. Academic Press. pp. 151–187.
1060:International Reviews of Immunology
802:10.1016/B978-0-12-800196-7.00008-6
235:major histocompatibility complexes
25:
893:10.2174/1574884712666170809124728
1308:10.1146/annurev.immunol.17.1.297
1209:Descotes, Jacques (March 2009).
792:. In Badylak, Stephen F. (ed.).
1135:Journal of Immunology Research
836:Advanced Drug Delivery Reviews
568:The Lancet Infectious Diseases
511:The Lancet Infectious Diseases
1:
1037:10.1016/s1734-1140(13)71467-1
881:Current Clinical Pharmacology
794:Host Response to Biomaterials
659:. World Health Organization.
626:10.1080/14760584.2019.1575734
580:10.1016/S1473-3099(19)30395-0
523:10.1016/S1473-3099(18)30490-0
116:Antigenic immunogenic potency
1108:10.1016/j.autrev.2017.04.002
690:"Lipid antigens in immunity"
404:10.1016/j.pervac.2011.05.005
1296:Annual Review of Immunology
391:Perspectives in Vaccinology
150:for cell-mediated immunity.
1372:
1279:10.1016/j.clim.2009.01.009
848:10.1016/j.addr.2009.07.001
1331:. Boca Raton: CRC Press.
1072:10.3109/08830189509061738
614:Expert Review of Vaccines
68:World Health Organization
432:10.1016/j.it.2007.07.011
250:antigen presenting cells
106:adaptive immune response
1025:Pharmacological Reports
928:Mayo Clinic Proceedings
299:Several innovations in
162:Antigen characteristics
471:10.4161/self.1.4.13904
356:Adaptive immune system
265:
1227:10.4161/mabs.1.2.7909
706:10.1515/hsz-2013-0220
387:"Vaccine development"
270:monoclonal antibodies
263:
256:Monoclonal antibodies
171:Phylogenetic distance
1148:10.1155/2016/1298473
1096:Autoimmunity Reviews
990:10.3390/antib8010021
694:Biological Chemistry
420:Trends in Immunology
278:Rheumatoid arthritis
1327:Atlas of Immunology
1267:Clinical Immunology
1253:http://www.e-i-p.eu
756:10.1155/2010/917075
324:In silico screening
313:chimeric antibodies
301:genetic engineering
1258:2023-12-06 at the
366:Host cell proteins
319:Evaluation methods
266:
1205:, p. 683–684
811:978-0-12-800196-7
666:978-92-4-069262-6
574:(11): 1235–1245.
194:Protein structure
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18:Antigenicity
217:to T cells)
215:MHC peptide
205:amino acids
130:conjugation
1356:Immunology
977:Antibodies
749:: 917075.
372:References
286:mast cells
197:Synthetic
148:immunogens
98:antibodies
983:(1): 21.
675:888748977
330:in silico
309:humanized
294:cytokines
110:immunogen
1350:Category
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1287:19269256
1256:Archived
1245:20061816
1167:27437405
1141:: 1–18.
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901:28799485
866:19619593
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634:30689467
598:31548079
549:58767762
541:30553695
489:21487506
440:17964218
351:Vaccines
345:See also
237:(MHC or
199:polymers
141:Proteins
132:with an
100:(a.k.a.
72:in vitro
51:pathogen
47:vaccines
1236:2725414
1158:4942633
1080:7494109
1000:6640699
949:2664605
857:7103283
766:3017905
715:4128234
589:6838664
480:3062386
184:density
182:Epitope
134:epitope
82:antigen
35:antigen
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227:T cell
122:lipids
86:hapten
905:S2CID
638:S2CID
545:S2CID
507:(PDF)
120:Many
1333:ISBN
1312:PMID
1283:PMID
1241:PMID
1215:mAbs
1199:ISBN
1189:In:
1163:PMID
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