250:
241:(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).
304:, 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.
325:
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
54:
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
269:. 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
321:
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.
326:
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.
600:
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".
329:
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.
93:). 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
1011:
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".
45:
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
1082:
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".
97:. 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
222:. 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
551:
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).
868:
Singh, Surjit; Kumar, Nitish K.; Dwiwedi, Pradeep; Charan, Jaykaran; Kaur, Rimplejeet; Sidhu, Preeti; Chugh, Vinay K. (9 October 2018). "Monoclonal
Antibodies: A Review".
492:
1283:
Porcelli, Steven A.; Modlin, Robert L. (April 1999). "THE CD1 SYSTEM: Antigen-Presenting
Molecules for T Cell Recognition of Lipids and Glycolipids".
317:
T cell epitope content, which is one of the factors that contributes to the risk of immunogenicity can now be measured relatively accurately using
293:
1254:
De Groot, Anne S.; Martin, William (May 2009). "Reducing risk, improving outcomes: Bioengineering less immunogenic protein therapeutics".
553:"Immunogenicity, effectiveness, and safety of measles vaccination in infants younger than 9 months: a systematic review and meta-analysis"
230:) molecules. Epitopes with higher binding affinities are more likely to be displayed on the surface of a cell. Because a T cell's
820:
798:
653:
234:
recognizes a specific epitope, only certain T cells are able to respond to a certain peptide bound to MHC on a cell surface.
819:
Weber, Constanze A.; Mehta, Preema J.; Ardito, Matt; Moise, Lenny; Martin, Bill; De Groot, Anne S. (30 September 2009).
1325:
1191:
779:"The Acquired Immune System Response to Biomaterials, Including Both Naturally Occurring and Synthetic Biomaterials"
223:
203:
237:
When protein drug therapeutics, (as in enzymes, monoclonals, replacement proteins) or vaccines are administered,
125:
such as a protein or polysaccharide to increase immunogenic potency so that they can evoke an immune response.
249:
132:
and few polysaccharides have immunogenic properties, which allows them to induce humoral immune responses.
42:, protecting the organism from future exposure. Immunogenicity is a central aspect of vaccine development.
493:"The efficacy, effectiveness, and immunogenicity of influenza vaccines in Africa: a systematic review"
117:
are relatively small molecules and/or have non-immunogenic properties. Consequently, they may require
677:
Dowds, C. Marie; Kornell, Sabin-Christin; Blumberg, Richard S.; Zeissig, Sebastian (1 January 2014).
318:
167: :- Molecules having bigger size, particularly those greater than10kDa, will be more immunogenic
56:
94:
238:
227:
1120:"Immunogenicity of Biotherapeutics: Causes and Association with Posttranslational Modifications"
1244:
344:
778:
407:
De Groot, Anne S.; Scott, David W. (November 2007). "Immunogenicity of protein therapeutics".
1314:
491:
Lindsey, Benjamin B; Armitage, Edwin P; Kampmann, Beate; de Silva, Thushan I (April 2019).
442:
Baker, Matthew; Reynolds, Helen M.; Lumicisi, Brooke; Bryson, Christine J. (October 2010).
266:
38:, where the injection of an antigen (the vaccine) provokes an immune response against the
8:
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301:
289:
258:
59:, immunogenicity should be investigated in a target population since animal testing and
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1199:
1146:
1119:
1047:
Lonberg, Nils; Huszar, Dennis (January 1995). "Human
Antibodies from Transgenic Mice".
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728:"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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444:"Immunogenicity of protein therapeutics: The key causes, consequences and challenges"
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Immunogenicity is influenced by multiple characteristics of an antigen:
821:"T cell epitope: Friend or Foe? Immunogenicity of biologics in context"
550:
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86:
30:
in the body of a human or other animal. It may be wanted or unwanted:
928:
282:
281:, causing allergy-like symptoms as well as the release of additional
274:
136:
98:
1010:
962:"Immunogenicity of Innovative and Biosimilar Monoclonal Antibodies"
726:
Stephen, Tom Li; Groneck, Laura; Kalka-Moll, Wiltrud Maria (2010).
373:
60:
39:
35:
77:) to bind specifically with a group of certain products that have
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Fishman, Jonathan M.; Wiles, Katherine; Wood, Kathryn J. (2015).
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122:
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23:
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has resulted in the decrease in immunogenicity, (also known as
262:
215:
74:
296:), of mAbs. Genetic engineering has led to the generation of
110:
16:
Ability of a foreign substance to provoke an immune response
1118:
Kuriakose, Anshu; Chirmule, Narendra; Nair, Pradip (2016).
676:
599:
441:
63:
models cannot precisely predict immune response in humans.
218:
epitope content is one of the factors that contributes to
202:
Degradability (ability to be processed & presented as
253:
725:
1241:
1184:
Immunobiology. The Immune System in Health and
Disease.
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1117:
959:
818:
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Doevendans, Erik; Schellekens, Huub (5 March 2019).
69:is the capacity of a chemical structure (either an
1313:
646:WHO Expert Committee on Biological Standardization
135:Proteins and some lipids/glycolypids can serve as
22:is the ability of a foreign substance, such as an
142:Proteins are significantly more immunogenic than
1336:
776:
261:(mAbs) are used for several diseases, including
104:
910:
814:
812:
810:
1282:
1253:
1182:, Paul Travers, Mark Walport, Mark Shlomchik:
55:changes with age. Therefore, as stated by the
1186:6th Edition. Garland Science, New York 2004,
1046:
406:
911:Schnyder, Benno; Pichler, Werner J. (2009).
807:
1312:Cruse, Julius M.; Lewis, Robert E. (1998).
34:Wanted immunogenicity typically relates to
1311:
150:
1223:
1200:"Immunotoxicity of monoclonal antibodies"
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273:(IgE) antibodies, which may bind onto
176:Chemical composition and heterogeneity
1240:The European Immunogenicity Platform
1176:Immunologists' Toolbox: Immunization.
732:International Journal of Microbiology
307:
913:"Mechanisms of Drug-Induced Allergy"
785:. Academic Press. pp. 151–187.
1049:International Reviews of Immunology
643:
13:
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791:10.1016/B978-0-12-800196-7.00008-6
224:major histocompatibility complexes
210:
14:
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882:10.2174/1574884712666170809124728
1297:10.1146/annurev.immunol.17.1.297
1198:Descotes, Jacques (March 2009).
781:. In Badylak, Stephen F. (ed.).
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861:
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1124:Journal of Immunology Research
825:Advanced Drug Delivery Reviews
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557:The Lancet Infectious Diseases
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500:The Lancet Infectious Diseases
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435:
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367:
1:
1026:10.1016/s1734-1140(13)71467-1
870:Current Clinical Pharmacology
783:Host Response to Biomaterials
648:. World Health Organization.
615:10.1080/14760584.2019.1575734
569:10.1016/S1473-3099(19)30395-0
512:10.1016/S1473-3099(18)30490-0
360:
105:Antigenic immunogenic potency
1097:10.1016/j.autrev.2017.04.002
679:"Lipid antigens in immunity"
393:10.1016/j.pervac.2011.05.005
7:
1285:Annual Review of Immunology
380:Perspectives in Vaccinology
333:
139:for cell-mediated immunity.
10:
1361:
1268:10.1016/j.clim.2009.01.009
837:10.1016/j.addr.2009.07.001
1320:. Boca Raton: CRC Press.
1061:10.3109/08830189509061738
603:Expert Review of Vaccines
57:World Health Organization
421:10.1016/j.it.2007.07.011
239:antigen presenting cells
95:adaptive immune response
1014:Pharmacological Reports
917:Mayo Clinic Proceedings
288:Several innovations in
151:Antigen characteristics
460:10.4161/self.1.4.13904
345:Adaptive immune system
254:
1216:10.4161/mabs.1.2.7909
695:10.1515/hsz-2013-0220
376:"Vaccine development"
259:monoclonal antibodies
252:
245:Monoclonal antibodies
160:Phylogenetic distance
1137:10.1155/2016/1298473
1085:Autoimmunity Reviews
979:10.3390/antib8010021
683:Biological Chemistry
409:Trends in Immunology
267:Rheumatoid arthritis
1316:Atlas of Immunology
1256:Clinical Immunology
1242:http://www.e-i-p.eu
745:10.1155/2010/917075
313:In silico screening
302:chimeric antibodies
290:genetic engineering
1247:2023-12-06 at the
355:Host cell proteins
308:Evaluation methods
255:
1194:, p. 683–684
800:978-0-12-800196-7
655:978-92-4-069262-6
563:(11): 1235–1245.
183:Protein structure
79:adaptive immunity
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48:adverse effects
28:immune response
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67:Antigenicity
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206:to T cells)
204:MHC peptide
194:amino acids
119:conjugation
1345:Immunology
966:Antibodies
738:: 917075.
361:References
275:mast cells
186:Synthetic
137:immunogens
87:antibodies
972:(1): 21.
664:888748977
319:in silico
298:humanized
283:cytokines
99:immunogen
1339:Category
1305:10358761
1276:19269256
1245:Archived
1234:20061816
1156:27437405
1130:: 1–18.
1105:28411169
1034:24399705
998:31544827
947:19252115
898:27211386
890:28799485
855:19619593
764:21234388
713:23999493
631:59338782
623:30689467
587:31548079
538:58767762
530:30553695
478:21487506
429:17964218
340:Vaccines
334:See also
226:(MHC or
188:polymers
130:Proteins
121:with an
89:(a.k.a.
61:in vitro
40:pathogen
36:vaccines
1225:2725414
1147:4942633
1069:7494109
989:6640699
938:2664605
846:7103283
755:3017905
704:4128234
578:6838664
469:3062386
173:density
171:Epitope
123:epitope
71:antigen
24:antigen
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263:cancer
216:T cell
111:lipids
75:hapten
894:S2CID
627:S2CID
534:S2CID
496:(PDF)
109:Many
1322:ISBN
1301:PMID
1272:PMID
1230:PMID
1204:mAbs
1188:ISBN
1178:In:
1152:PMID
1128:2016
1101:PMID
1065:PMID
1030:PMID
994:PMID
943:PMID
886:PMID
851:PMID
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760:PMID
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