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

• Published in: Toxicon (Oxford) 2015-09, Vol.103, p.135-144
• Main Authors: Lukić, Ivana, Marinković, Emilija, Filipović, Ana, Krnjaja, Ognjen, Kosanović, Dejana, Inić-Kanada, Aleksandra, Stojanović, Marijana
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Antibodies, Monoclonal - blood; Antibodies, Monoclonal - immunology; Antibody Affinity; Binding characteristics; Biocompatibility; Biomedical materials; Gangliosides - blood; Half-Life; In vitro testing; In vivo testing; In vivo tests; Mice; Monoclonal antibody; Protection; Protein Binding; Surgical implants; Tetanus - immunology; Tetanus - prevention & control; Tetanus Antitoxin - blood; Tetanus Antitoxin - immunology; Tetanus toxin; Tetanus Toxin - antagonists & inhibitors; Tetanus Toxin - immunology; Toxins
• ISSN: 0041-0101; 1879-3150
• DOI: 10.1016/j.toxicon.2015.06.025

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 × 108 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. •Eight monoclonal anti-tetanus toxin antibodies characterized in vitro and their protective potential assessed in vivo.•No single in vitro tested parameter, which could be used alone to select protective anti-tetanus toxin antibodies.•Required parameter combination: the affinity of ≥1 × 108 M−1 and the ability to prevent TTn –ganglioside interaction.