TLRs are excellent targets for such multi-epitope vaccines to provide a signal to induce an effective immune response that in turn leads to long-lasting protection . The protocol used for the search for multi-epitope modulators is substantially different from the one used for smallmolecule modulators. The general protocol consists of multiple steps: i) retrieval of target proteins sequences, ii) evaluation of antigenic and physicochemical properties of the target proteins, iii) epitopes prediction, iv) multi-epitope vaccine construction, v) evaluation of antigenicity and allergenicity of the vaccine combined with the exploration of the physicochemical parameters, vi) prediction of secondary and tertiary structure, vii) molecular docking to the immune receptors, and viii) dynamics' analysis of the complexes. Some studies also include further computational immune simulation to assess the vaccine's ability to stimulate the immune response (Figure ). Each step of this protocol is quite elaborate and usually requires the usage of several tools/servers. As information about vaccine construction has not previously been addressed in computational reviews about TLRs, a brief summary is given here. Target sequences might be obtained from databases like PDB or UniProt . Then, they are submitted e.g. to the VaxiJen to check the antigenicity and to ExpasyProtParam to investigate the physicochemical properties.