The use of Bacillus subtilis as a cost-effective expression system for production of Cholera Toxin B fused factor VIII epitope regions applicable for inducing oral immune tolerance - Sorbonne Université
Article Dans Une Revue Folia Microbiologica Année : 2024

The use of Bacillus subtilis as a cost-effective expression system for production of Cholera Toxin B fused factor VIII epitope regions applicable for inducing oral immune tolerance

Résumé

Coagulation factor replacement therapy for the X-linked bleeding disorder Haemophilia, characterized by a deficiency of coagulation protein factor VIII (FVIII), is severely complicated by antibody (inhibitors) formation. The development of FVIII inhibitors drastically alters the quality of life of the patients and is associated with a tremendous increase in morbidity as well as treatment costs. The ultimate goal of inhibitor control is antibody elimination. Immune tolerance induction (ITI) is the only clinically established approach for developing antigen-specific tolerance to FVIII. This work aims to establish a novel cost-effective strategy to produce FVIII molecules in fusion with cholera toxin B (CTB) subunit at the N terminus using the Bacillus subtilis expression system for oral tolerance, as the current clinical immune tolerance protocols are expensive. Regions of B-Domain Deleted (BDD)-FVIII that have potential epitopes were identified by employing Bepipred linear epitope prediction; 2 or more epitopes in each domain were combined and cDNA encoding these regions were fused with CTB and cloned in the Bacillus subtilis expression vector pHT43 and expression analysis was carried out. The expressed CTB-fused FVIII epitope domains showed strong binding affinity towards the CTB-receptor GM1 ganglioside. To conclude, Bacillus subtilis expressing FVIII molecules might be a promising candidate for exploring for the induction of oral immune tolerance.
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Dates et versions

hal-04784505 , version 1 (15-11-2024)

Identifiants

Citer

Vijay Elakkya Vijayakumar, Mookambeswaran Vijayalakshmi, Sébastien Lacroix-Desmazes, Krishnan Venkataraman. The use of Bacillus subtilis as a cost-effective expression system for production of Cholera Toxin B fused factor VIII epitope regions applicable for inducing oral immune tolerance. Folia Microbiologica, 2024, 69 (6), pp.1267-1277. ⟨10.1007/s12223-024-01166-z⟩. ⟨hal-04784505⟩
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