Design of a Multi-Epitope Vaccine Candidate Against Infectious Laryngotracheitis Virus Affecting Poultry by Computational Approaches

Abstract

Infectious laryngotracheitis (ILT) is a severe upper respiratory disease highly contagious in chickens that causes a huge economic impact on the poultry industry all over the world. The current study aimed to design a multi-epitope-based vaccine candidate using envelope glycoprotein B and glycoprotein D of the ILT virus using an immune informatics approach. The glycoproteins B and D are crucial for attachment as well as entry of ILT virus inside the cell, which makes them a potential option for designing vaccine candidates. The prediction of epitopes, viz. helper T lymphocyte, cytotoxic T lymphocyte and interferon-gamma producing epitopes, was performed and high-scoring predicted epitopes were joined in an organized manner using suitable linkers to design the final vaccine candidate. The avian beta-defensin 1 was included as an adjuvant in the amino-terminal of the vaccine design that possesses antimicrobial activity and histidine residues at the carboxy-terminal for the purpose of purification. The final vaccine candidate was evaluated for its physicochemical characteristics, solubility, antigenicity, stability, and allergenicity and validated for its modeling. Molecular docking, binding affinity, and interacting residues between the vaccine candidate and immune receptors, viz. TLR 3, MHC Class I and Class II were assessed. Further, to assess the immune response profile generated by the final vaccine design, an insilico immune simulation study was also performed. The findings of this study revealed that the final vaccine candidate was antigenic, nonallergenic, stable, interacted with immune receptors, and able to produce antibodies as well as cellular immune responses against ILTV infection.

Keywords: avian beta-defensin 1; glycoprotein B; glycoprotein D; immunoinformatics; infectious laryngotracheitis virus; multi-epitope vaccine.

Figure 1

Tertiary structure of glycoprotein B and glycoprotein D of ILTV.

Figure 2

Mapping of predicted CTL epitopes in the 3D structure of glycoprotein B of ILTV.

Figure 3

Mapping of predicted CTL epitopes in the 3D structure of glycoprotein D of ILTV.

Figure 4

Mapping of predicted HTL epitopes in the 3D structure of glycoprotein B of ILTV.

Figure 5

Mapping of predicted HTL epitopes in the 3D structure of glycoprotein D of ILTV.

Figure 6

Design of multi-epitope final vaccine construct against ILTV.

Figure 7

Secondary structure of the multi-epitope final vaccine construct against ILTV.

Figure 8

A 3D model of the multi-epitope final vaccine construct against ILTV.

Figure 9

Validation of a 3D model of multi-epitope final vaccine construct (a) Validation of structure by ERRAT (b) Validation of structure by ProSA (c) Validation of structure by ProSA—Local model quality (d) Validation of a 3D model of final vaccine construct by Ramachandran Plot analysis.

Figure 10

Molecular docking of the final multi-epitope vaccine with TLR3.

Figure 11

Molecular docking of the final multi-epitope vaccine with Class II MHC and Class I MHC.

Figure 12

(a) Interacting residues between the final multi-epitope vaccine with TLR 3 (b), Interacting residues between the final multi-epitope vaccine with class I MHC (c),and Interacting residues between the final multi-epitope vaccine with class II MHC.

Figure 12

(a) Interacting residues between the final multi-epitope vaccine with TLR 3 (b), Interacting residues between the final multi-epitope vaccine with class I MHC (c),and Interacting residues between the final multi-epitope vaccine with class II MHC.

Figure 13

(a–r) Immune simulation studies of the final vaccine construct.

Figure 13

(a–r) Immune simulation studies of the final vaccine construct.

Figure 13

(a–r) Immune simulation studies of the final vaccine construct.