Key protection factors against tetanus: Anti-tetanus toxin antibody affinity and its ability to prevent tetanus toxin - ganglioside interaction
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2015
Authors
Lukić, IvanaMarinković, Emilija
Filipović, Ana
Krnjaja, Ognjen
Kosanović, Dejana
Inić-Kanada, Aleksandra
Stojanović, Marijana
Article (Published version)
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Antibodies capable to neutralize tetanus toxin (TeNT) are key factors in protection against tetanus disease. Although antibody-based therapeutics for treatment of tetanus exist on the market its production is tedious. Hence, the tetanus-specific antibodies preparation that could be easily produced in large scale in vitro would be beneficial. Monoclonal antibodies (MAbs) are considered for a long time as a reagent of choice, but the core drawback is how to select a MAb that would be safe in providing efficacious protection. In this study we have investigated the parameters crucial for a single MAb to be assigned as protective. Eight murine MAbs were characterized in vitro for their reactivity toward TeNT and assessed in vivo for protectiveness against TeNT intoxication. Correlation of in vitro and in vivo data has revealed that in vitro selection of MAb that is protective in vivo could be performed by a combination of two assays: the measurement of MAb affinity toward TeNT taking Ka 1 x... 10(8) M-1 as a threshold level, and the evaluation of its capability to prevent TeNT-ganglioside interaction. Single MAb could be taken into consideration as a potential therapeutic only if it has a capacity to completely inhibits TeNT-ganglioside complex formation. (C) 2015 Elsevier Ltd. All rights reserved.
Keywords:
Tetanus toxin / Monoclonal antibody / Binding characteristics / ProtectionSource:
Toxicon, 2015, 103, 135-144Publisher:
- Pergamon-Elsevier Science Ltd, Oxford
Funding / projects:
- Allergens, antibodies, enzymes and small physiologically important molecules: design, structure, function and relevance (RS-MESTD-Basic Research (BR or ON)-172049)
DOI: 10.1016/j.toxicon.2015.06.025
ISSN: 0041-0101
PubMed: 26140841
WoS: 000359888300018
Scopus: 2-s2.0-84936886268
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TorlakTY - JOUR AU - Lukić, Ivana AU - Marinković, Emilija AU - Filipović, Ana AU - Krnjaja, Ognjen AU - Kosanović, Dejana AU - Inić-Kanada, Aleksandra AU - Stojanović, Marijana PY - 2015 UR - http://intor.torlakinstitut.com/handle/123456789/425 AB - Antibodies capable to neutralize tetanus toxin (TeNT) are key factors in protection against tetanus disease. Although antibody-based therapeutics for treatment of tetanus exist on the market its production is tedious. Hence, the tetanus-specific antibodies preparation that could be easily produced in large scale in vitro would be beneficial. Monoclonal antibodies (MAbs) are considered for a long time as a reagent of choice, but the core drawback is how to select a MAb that would be safe in providing efficacious protection. In this study we have investigated the parameters crucial for a single MAb to be assigned as protective. Eight murine MAbs were characterized in vitro for their reactivity toward TeNT and assessed in vivo for protectiveness against TeNT intoxication. Correlation of in vitro and in vivo data has revealed that in vitro selection of MAb that is protective in vivo could be performed by a combination of two assays: the measurement of MAb affinity toward TeNT taking Ka 1 x 10(8) M-1 as a threshold level, and the evaluation of its capability to prevent TeNT-ganglioside interaction. Single MAb could be taken into consideration as a potential therapeutic only if it has a capacity to completely inhibits TeNT-ganglioside complex formation. (C) 2015 Elsevier Ltd. All rights reserved. PB - Pergamon-Elsevier Science Ltd, Oxford T2 - Toxicon T1 - Key protection factors against tetanus: Anti-tetanus toxin antibody affinity and its ability to prevent tetanus toxin - ganglioside interaction EP - 144 SP - 135 VL - 103 DO - 10.1016/j.toxicon.2015.06.025 ER -
@article{ author = "Lukić, Ivana and Marinković, Emilija and Filipović, Ana and Krnjaja, Ognjen and Kosanović, Dejana and Inić-Kanada, Aleksandra and Stojanović, Marijana", year = "2015", abstract = "Antibodies capable to neutralize tetanus toxin (TeNT) are key factors in protection against tetanus disease. Although antibody-based therapeutics for treatment of tetanus exist on the market its production is tedious. Hence, the tetanus-specific antibodies preparation that could be easily produced in large scale in vitro would be beneficial. Monoclonal antibodies (MAbs) are considered for a long time as a reagent of choice, but the core drawback is how to select a MAb that would be safe in providing efficacious protection. In this study we have investigated the parameters crucial for a single MAb to be assigned as protective. Eight murine MAbs were characterized in vitro for their reactivity toward TeNT and assessed in vivo for protectiveness against TeNT intoxication. Correlation of in vitro and in vivo data has revealed that in vitro selection of MAb that is protective in vivo could be performed by a combination of two assays: the measurement of MAb affinity toward TeNT taking Ka 1 x 10(8) M-1 as a threshold level, and the evaluation of its capability to prevent TeNT-ganglioside interaction. Single MAb could be taken into consideration as a potential therapeutic only if it has a capacity to completely inhibits TeNT-ganglioside complex formation. (C) 2015 Elsevier Ltd. All rights reserved.", publisher = "Pergamon-Elsevier Science Ltd, Oxford", journal = "Toxicon", title = "Key protection factors against tetanus: Anti-tetanus toxin antibody affinity and its ability to prevent tetanus toxin - ganglioside interaction", pages = "144-135", volume = "103", doi = "10.1016/j.toxicon.2015.06.025" }
Lukić, I., Marinković, E., Filipović, A., Krnjaja, O., Kosanović, D., Inić-Kanada, A.,& Stojanović, M.. (2015). Key protection factors against tetanus: Anti-tetanus toxin antibody affinity and its ability to prevent tetanus toxin - ganglioside interaction. in Toxicon Pergamon-Elsevier Science Ltd, Oxford., 103, 135-144. https://doi.org/10.1016/j.toxicon.2015.06.025
Lukić I, Marinković E, Filipović A, Krnjaja O, Kosanović D, Inić-Kanada A, Stojanović M. Key protection factors against tetanus: Anti-tetanus toxin antibody affinity and its ability to prevent tetanus toxin - ganglioside interaction. in Toxicon. 2015;103:135-144. doi:10.1016/j.toxicon.2015.06.025 .
Lukić, Ivana, Marinković, Emilija, Filipović, Ana, Krnjaja, Ognjen, Kosanović, Dejana, Inić-Kanada, Aleksandra, Stojanović, Marijana, "Key protection factors against tetanus: Anti-tetanus toxin antibody affinity and its ability to prevent tetanus toxin - ganglioside interaction" in Toxicon, 103 (2015):135-144, https://doi.org/10.1016/j.toxicon.2015.06.025 . .