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, TC cell, and TH 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

Identification and prioritisation of potential vaccine candidates using subtractive proteomics and designing of a multi-epitope vaccine against Wuchereria bancrofti

“…Vaccines have the potential to provide long-lasting protection, target multiple stages of the parasite's life cycle, and complement existing control measures 18 – 20 . Extensive research efforts have been dedicated to identifying suitable vaccine candidates using various approaches, including subtractive genomics and reverse vaccinology 21 – 24 .…”