Sulfavants, new class of molecular vaccine adjuvants: development in immunotherapy and correlation of the colloidal self-assempbly with immune cell response

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 [1]. Sulfavant A is able to prime human DCs by a TLR2/TLR4-independent mechanism inducing maturation of DC with expression of high levels of MHC II molecules and upregulation of costimulatory proteins (CD83, CD86) and proinflammatory cytokines (IL-12 and INF-?) [1]. Moreover 1 triggers an efficient immune response in vivo; in fact mice immunized with OVA associated to Sulfavant A (1:500) produced a titer of anti-OVA Ig comparable to traditional adjuvants. In an experimental model of melanoma, vaccination of C57BL/6 mice by Sulfavant A-adjuvanted hgp10 peptide elicited a protective response with reduction of tumour growth and increase of survival. Improved synthesis of the sulfolipid scaffold, the preparation of two epimeric analogs named Sulfavant-S (2) and Sulfavant-R (3), as well as a study of self-aggregation of these molecule in water and the effect of this aggregation on biological response will be the object of this communication [2]. In the new synthetic approach, the strategy for Sulfavant A is reduced from 14 to 11 steps with approximately triplication of the overall yield (11%) permitting the preparation of the analogs 2-3 [2]. The new members Sulfavant R and S elicit dendritic cells (DC) maturation at a concentration of 10 nM, which is 1000 times lower than that of the parent molecule 1. Analysis by Dynamic Light Scattering (DLS) indicates self-assembly of Sulfavants and formation of colloidal particles with a small hydrodynamic radius (Rh~60 nm) for the epimers 2 and 3, and a larger radius (Rh~150 nm) for 1. Further studies on these aggregates by Small Angle Neutron Scattering (SANS) and Zeta potential analysis suggest that the equilibrium between colloidal aggregates and free monomers determines the effective concentration of the sulfolipid molecule at the cellular targets and affects the immunological efficacy of 1-3. Sulfavants 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.