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Key protection factors against tetanus: Anti-tetanus toxin antibody affinity and its ability to prevent tetanus toxin - ganglioside interaction

Authorized Users Only
2015
Authors
Lukić, Ivana
Marinković, Emilija
Filipović, Ana
Krnjaja, Ognjen
Kosanović, Dejana
Inić-Kanada, Aleksandra
Stojanović, Marijana
Article (Published version)
Metadata
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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.

Keywords:
Tetanus toxin / Monoclonal antibody / Binding characteristics / Protection
Source:
Toxicon, 2015, 103, 135-144
Publisher:
  • Pergamon-Elsevier Science Ltd, Oxford
Funding / projects:
  • Allergens, antibodies, enzymes and small physiologically important molecules: design, structure, function and relevance (RS-172049)

DOI: 10.1016/j.toxicon.2015.06.025

ISSN: 0041-0101

PubMed: 26140841

WoS: 000359888300018

Scopus: 2-s2.0-84936886268
[ Google Scholar ]
11
10
URI
http://intor.torlakinstitut.com/handle/123456789/425
Collections
  • Radovi istraživača / Researchers’ publications
Institution/Community
Torlak
TY  - 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
UR  - conv_365
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",
url = "conv_365"
}
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
conv_365
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
conv_365 .
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 .,
conv_365 .

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