Background: Lymphatic filariasis is a neglected tropical disease (NTD) affecting more than 863 million people in 47 countries across the world. A multi-epitope prophylactic/therapeutic vaccination targeting filarial defense proteins would be invaluable in achieving the current goal of LF elimination.

Method: In this study, a combination of immunomics and immune-informatics was applied to construct a multi-epitope vaccine candidate. The antigenic proteins were identified by immune blotting against different categories of Wuchereria bancrofti-infected LF sera.

Result: The major antigenic proteins were heat shock protein 70, Tubulin beta chain, Enolase, Galectin, and 14-3-3 zeta. The five antigens were combined together to construct a multi-epitope vaccine after predicting the linear B-cell and T-cell epitopes of individual antigens. A three-dimensional model of the candidate vaccine was predicted, followed by refinement, and was validated using RAMPAGE and PROCHECK servers. A Toll-like receptor (TLR) agonist, a 50S ribosomal subunit of Mycobacterium tuberculosis, was included in the candidate vaccine to enhance vaccine immunogenicity. The docking of the chimeric peptide vaccine against the TLR5 resulted in high binding efficiency for the docked complex. The in silico immune simulation provided a significant increase in CD4⁺ T-cell and CD8⁺ T-cell populations.

Conclusion: In summary, the recombinant putative vaccine showed high immunogenicity which could be experimentally validated in the future for the development of a potent LF vaccine. Furthermore, by employing multi-epitope structures and constructing a cocktail vaccine for LF, this study has the potential to represent an important milestone in the development of an anti-filarial vaccine.