Adjuvants are components of vaccine that enhance the specific immune response against co-inoculated antigens. Recently, we reported the characterization of a synthetic sulfolipid named Sulfavant A (1) as a promising candidate of a novel class of molecular adjuvants based on the sulfoquinovosyl-diacylglycerol skeleton. Here, we report an improved synthesis of the sulfolipid scaffold, as well as the preparation of two analogs named Sulfavant-S (2) and Sulfavant-R (3) with enhanced property to modulate master immune targets such as human dendritic cells (DCs). According to the present approach, synthesis of 1 is reduced from 14 to 11 steps with nearly triplication of the overall yield (11%). The new members 2 and 3 elicit DC maturation at a concentration of 10 nM, which is 1000 times more potent than the parent molecule 1. Analysis of dynamic light scattering indicates self-assembly of Sulfavants and formation of colloidal particles with a small hydrodynamic radius (50 nm) for the epimers 2 and 3 and a larger radius (150 nm) for 1. The colloidal aggregates are responsible for the bell-shaped dose-response curve of these products. We conclude that the particle size also affects the equilibrium with free monomers, thus determining the effective concentration of the sulfolipid molecule at the cellular targets and the different immunological efficacy of 1-3. Sulfavants (1-3) do not show in vitro cytotoxicity at concentrations 105 higher than the dose that triggers maximal immune response, thus predicting a low level of toxicological risk in their formulation in vaccines.