Targeting Mitogen-Activated Protein Kinase-Activating Death Domain Protein of Brugia malayi for Construction of a Multi-Epitope Subunit Vaccine Against Lymphatic Filariasis

Abstract

Background

Lymphatic filariasis (LF) is a disease caused by parasitic worms that can lead to a debilitating condition known as elephantiasis. According to the World Health Organization, 657 million people across 39 countries are at risk of contracting LF. Eliminating LF remains a challenge despite ongoing efforts, primarily due to the ineffectiveness of existing treatments and the rise of drug resistance. Currently, no vaccines are available for LF. The main objective of this study was to design a vaccine that targets the MAP kinase-activating death domain (MADD) protein of Brugia malayi.

Methods

Employing an in silico approach, we screened proteins to identify B- and T-cell epitopes and assess their safety. These epitopes were combined with adjuvants and linkers to design a multi-epitope vaccine. The six resulting vaccine models were refined using the GalaxyRefine tool to determine the most stable vaccine candidate, which was further validated through molecular dynamic simulations. Immune simulations were carried out using the final selected vaccine candidate.

Results

Here, we show significant stimulation of humoral and cell-mediated immune responses resulting in the production of numerous memory B cells and T cells and a substantial increase in the production of the IgG1 antibody. These antibodies are crucial in clearing microfilariae from the peripheral circulation of infected individuals.

Conclusion

Our findings highlight MADD protein as a promising vaccine candidate to target LF.