Peptide secondary structures can be harnessed to design monomers capable of self-assembling into supramolecular polymers in aqueous media. Decorating the surface with immunogenic molecular patterns results in pathogen-mimicking entities and potential vaccine candidates. In the context of antitumor vaccines, the challenge is to overcome self-tolerance mechanisms to enforce an immune response against endogenous, tumor-associated glycopeptide motifs. To this end, a co-stimulation of B cells with Th cells is mandatory, which we aim to achieve using a co-presentation of different epitopes and immunostimulating agents at the surface of multicomponent supramolecular polymers. Mucin 1 (MUC1) is well-known for undergoing alterations in O-glycosylation during tumorigenesis, and is thus an excellent tumor-associated target structure for immunotherapy. In this contribution I focus on the use a fully synthetic glycopeptide from the MUC1 tandem repeat sequence. As T cell epitope we chose a small fragment from highly immunogenic tetanus toxin (p30). Additionally, an imidazoquinoline as potent TLR7/8 agonist, was synthesized. These epitopes were conjugated to supramolecular monomers and mixed in aqueous solution to yield a polymeric vaccine formulation. High antibody titers of the IgG type were observed in C57BL/6 mice and FACS analysis confirmed the high binding affinity of the antibodies to T47D tumor cells. These results support the potential of this modular supramolecular platform approach for the development of glycoconjugate vaccines.

Multicomponent supramolecular polymers as a platform for the design of glycoconjugate vaccines

ACS Fall 2021

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