Targeting delivery of tumor-associated carbohydrate antigen(TACA)-based vaccine to antigen-presenting cells(APCs)mediated by endogenous antibodies can improve the immunogenicity of TACA.However,an essential requirement of this approach is to generate high titers of endogenous antibodies in vivo through pre-immunization,which complicates the immunization procedure and may cause side effects.Herein,we report a new generation of APC-targeting TACA-based supramolecular complex vaccine,as-sembled by sialyl Thomsen-nouveau-bovine serum albumin-adamantine(sTn-BSA-Ada)and heptavalent rhamnose(Rha)-modified β-cyclodextrin(β-CD)via host-guest interaction.The complex vaccine re-tained anti-Rha antibodies recruiting capability and facilitated the APCs uptake of the vaccine via the interaction of the Fc-domain with the Fc receptors on APCs.We demonstrate that direct immuniza-tion of complex vaccine elicited anti-Rha and anti-sTn specific immune response synchronously,gen-erating a novel self-enhancement effect that can improve the antigen delivery to APCs in high efficacy.The structure-activity relationship(SAR)study proved that complex vaccine 4 with polyethylene glycol 6(PEG6)linker in host molecule provoked a robust and specific sTn immune response comparable to the pre-immunization approach.The antisera induced by complex vaccine,either through direct immuniza-tion or pre-immunization,exhibited equal potency of cytotoxicity against the sTn expression cancer cells.This study provides a general platform for TACA-based vaccines with self-enhancement effects without the need for pre-immunization.
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维普
