Supramolecular complex glycoconjugate vaccine generates self-enhancement effects for carbohydrate antigen delivery  

作　　者：Han Lin Yanchun Li Kun Zhou Dan Li Hangyan Yu Jie Zhao Haofei Hong Zhifang Zhou Zhimeng Wu 

机构地区：[1]Key Laboratory of Carbohydrate Chemistry & Biotechnology,Ministry of Education,School of Biotechnology,Jiangnan University,Wuxi 214122,China

出　　处：《Chinese Chemical Letters》2024年第2期317-322,共6页中国化学快报（英文版）

基　　金：supported by the National Natural Science Foundation of China(No.22177040);the Natural Science Foundation of Jiangsu Province(No.BK20200601);partly funded by the 111 Project(No.111-2-06).

摘　　要：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,assembled by sialyl Thomsen-nouveau-bovine serum albumin-adamantine(sTn-BSA-Ada)and heptavalent rhamnose(Rha)-modifiedβ-cyclodextrin(β-CD)via host-guest interaction.The complex vaccine retained 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 immunization of complex vaccine elicited anti-Rha and anti-sTn specific immune response synchronously,generating 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(PEG 6)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 immunization 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.

关 键 词：Glycoconjugate vaccine Endogenous antibody APC-targeting Supramolecular complex sTn antigen 

分 类 号：TQ460.1[化学工程—制药化工]