Computational evaluation of a fusion protein consisted of pertussis toxin and filamentous hemagglutinin fromBordetella pertussisto target Claudin-4 using C-terminal fragment ofClostridium perfringensenterotoxin

Pertussis, caused byBordetella pertussisis still one of the controversial diseases worldwide due to its high prevalence in both the developed and the developing countries, especially among young children. As currently approved vaccines are not protective enough and provide Th2-type immune responses, there is an urgent need to develop new vaccines. In the current study, we applied the C-terminal fragment ofClostridium perferingensenterotoxin (C-CPE) as a delivery system and F1S1 fragment (Filamentous hemagglutinin (F1) and subunit 1 of pertussis toxin (S1) ofB. pertussisto design a novel chimeric proteinin silico, to target Claudin-4 receptors in mice lung cells. To achieve this goal, the primary, secondary and tertiary structures of the fusion protein were evaluated and the interaction of this protein with Claudin-4 receptors was studied. Molecular dynamic (MD) simulation analysis was performed to investigate the physical movement of atoms in a fixed period. According to the results; the full-length fusion protein has consisted of 807 amino acid residues which could be classified as a stable protein. There was a convenient consistency between the 3D predicted structure and the secondary structure prediction. An acceptable percentage of the residues were also detected in the most favored and allowed regions for the model. Based on HADDOCK results, there were no considerable differences between the interactions and MD simulation analysis, indicating that the predicted structures were stable during the simulation. Altogether, the data reported in this study represents the first step toward developing a nasal vaccine candidate againstB. pertussisinfection. Communicated by Ramaswamy H. Sarma

Automated summary

This study designed a novel chimeric protein using C-CPE as a delivery system and F1S1 fragment of B. pertussis to target Claudin-4 receptors in mice lung cells. Molecular dynamic simulation showed the fusion protein had a stable structure, suggesting its potential as a vaccine candidate against B. pertussis infection.