Vaccines (Oct 2022)

Designing of Peptide Based Multi-Epitope Vaccine Construct against Gallbladder Cancer Using Immunoinformatics and Computational Approaches

  • Mukhtar Ahmad Dar,
  • Pawan Kumar,
  • Prakash Kumar,
  • Ashish Shrivastava,
  • Muneer Ahmad Dar,
  • Richa Chauhan,
  • Vinita Trivedi,
  • Ashutosh Singh,
  • Eshan Khan,
  • Ravichandiran Velayutham,
  • Sameer Dhingra

DOI
https://doi.org/10.3390/vaccines10111850
Journal volume & issue
Vol. 10, no. 11
p. 1850

Abstract

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Gallbladder cancer (GBC) is an aggressive and difficult to treat biliary tract carcinoma with a poor survival rate. The aim of this study was to design a peptide-based multi-epitope vaccine construct against GBC using immunoinformatics approaches. Three proteins implicated in the progression of GBC were selected for B and T cell epitope prediction and the designing of the potential vaccine construct. Seven CTL, four HTL and six Bcell epitopes along with a suitable adjuvant were selected and connected using linkers for designing the vaccine construct. The secondary and tertiary models of the designed vaccine were generated and satisfactorily validated. A Ramachandran plot of the final 3D model showed more than 90% of the residues in allowed regions and only 0.4% in disallowed regions. The binding affinity of a vaccine construct with TLR 2, 3 and 4 receptors was assessed through molecular docking and simulation. The average numbers of hydrogen bonds for vaccine-TLR 2, 3 and 4 complexes in the simulation were 15.36, 16.45, and 11.98, respectively, and remained consistent over a 100 ns simulation period, which is critical for their function. The results of this study provide a strong basis for further evaluation through in vitro/in vivo experimental validation of the safety and efficacy of the designed vaccine construct.

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