The research discussed here enables vaccinologists to choose from a large panel of adjuvants and formulate them in combinations that act cooperatively, resulting in optimal protection. We have developed adjuvants, rationally designed based on the current understanding of the immune response, particularly the molecular mechanism of the innate immune response. The term adjuvant is often interchangeable with immunostimulant. Whereas immunostimulants are generally single compounds with intrinsic immunogenicity, adjuvants can be a mixture of different components. These components can have different functions and activities, including carrier or targeting functions and immunostimulant and immunomodulatory properties. The current challenge facing adjuvant development is finding the optimal combination of the different components that act synergistically and induce the desired immune response. Recent advances in biochemical tools have enabled us to design and develop such adjuvants. This study explores two new ways of designing and developing adjuvants. First, we demonstrate that combining multiple PRR ligands (three) into a single molecule using chemical conjugation amplified the immune response compared to the soluble mixture of ligands. Secondly, we showed that incorporating immunomodulators and immunostimulants into the same molecular scaffold improves the molecule’s safety profile and the protection it affords.