Multimeric antigen display and high overall valency are increasingly regarded as strategic goals for potent and broadly efficacious synthetic vaccines with potential market prospects. Herein, a modular and versatile approach to multifunctional peptide-based vaccine platforms at multimilligram scale in reasonable yields is reported. Preparation of chemoselectively modified peptide building blocks of medium-to-large size, conjugation of these subunits, and final assembly were achieved by a combination of Michael-type thiol-ene addition and copper(I)-mediated alkyne-azide cycloaddition. The size and structural complexity of the building blocks required exploration of a further level of orthogonality, namely furan/maleimide Diels-Alder chemistry. After process optimization, a finely tuned, stepwise click approach has emerged as a workable, on-demand strategy to create macromolecular therapeutic vaccine assemblies.