Construction and validation of a multi-epitope in silico vaccine model for lymphatic filariasis by targeting Brugia malayi: a reverse vaccinology approach

Abstract

Background

Lymphatic filariasis (LF), often referred to as elephantiasis, has been identified as one of the 17 neglected tropical diseases by the World Health Organization. Currently, there are no vaccines available to treat this infection in humans. Therefore, with the objective of devising a novel preventive measure, we exploited an immunoinformatics approach to design a multi-epitope-based subunit vaccine for LF, that can elicit a variety of immune responses within the host. In this study, different B cell, T _C cell, and T _H cell-binding epitopes were screened from the antigenic proteins of Brugia malayi and they were passed through several immunological filters to determine the optimal epitopes.

Results

As a result, 15 CD8+, 3 CD4+, and 3 B cell epitopes were found to be prominent, antigenic, non-toxic, immunogenic and non-allergenic. The presence of conformational B cell epitopes and cytokine-inducing epitopes confirmed the humoral and cell-mediated immune response that would be triggered by the constructed vaccine model. Following that, the selected epitopes and TLR-4-specific adjuvant were ligated by appropriate peptide linkers to finalize the vaccine construct. Protein–protein docking of the vaccine structure with the TLR4 receptor predicted strong binding affinity and hence putatively confirms its ability to elicit an immune response. Further, the efficiency of the vaccine candidate to provide a long-lasting protective immunity was assessed by in silico immune simulation. The reverse translated vaccine sequence was also virtually cloned in the pET28a (+) plasmid after the optimization of the gene sequence.

Conclusion

So taken together, by monitoring the overall in silico assessment, we hypothesize that our engineered peptide vaccine could be a viable prophylactic approach in the development of vaccines against the threat of human lymphatic filariasis.

Graphical Abstract

Supplementary Information

The online version contains supplementary material available at 10.1186/s42269-023-01013-0.

Highlights

• A novel computational approach was adopted for the development of a vaccine model against lymphatic filariasis.

• The potential epitopes were screened to test their antigenicity, toxicity, immunogenicity, and allergenicity.

• The prophylactic vaccine model was constructed with appropriate peptide linkers and the adjuvant—50 s ribosomal protein L7/L12.

• The tertiary structure of the vaccine model was validated with Ramachandran plot, ProSA, etc.

• Molecular docking against TLR4 receptor and immune simulation studies were performed to test the efficacy of the vaccine.

Supplementary Information

The online version contains supplementary material available at 10.1186/s42269-023-01013-0.