CONTEXT: Multi-epitope vaccine (MEV) construction is a technique which combines multiple epitopes, both B cell epitopes and T cell epitopes which have the potential to elicit a much stronger immune response compared to a subunit vaccine. Therefore, recently, a lot of research has been focused on development and improvement of multiepitope vaccines. The strategy of designing a MEV in silico lies in a few basic steps, including procuring the amino acid sequence of the B cell and T cell epitopes from literature search, bioinformatics approach, to construct a potent immunogen capable of eliciting both humoral and cell-mediated response and finally joining these epitopes by linkers. However, a vaccine constructed by merely joining the epitopes may not always result in a stable globular structured protein. In this study, we have focused on developing a strategy where a potential vaccine candidate of Mycobacterium tuberculosis has been used as a scaffold and the low complexity regions of this scaffold have been replaced by the predicated epitopes. Essentially, instead of joining the epitopes by linkers, they have been carefully positioned on a scaffold of a protein that is itself a vaccine candidate to derive a MEV against Mycobacterium tuberculosis. METHOD: In this study, a methodology has been detailed to tackle this great challenge using a simple approach of protein engineering. A scaffold-based MEV has been designed against Mtb by converting a vaccine candidate protein, Ag85A, into a scaffold by truncating its low complexity non-immunogenic regions, and the gaps were supplemented by the highly immunogenic epitopes. Replicated 500 ns molecular dynamics simulation at different temperatures (300 K and 310 K) and principal component analysis proved that MEV built on the scaffold is more stable than the conventional one.