Department of Biomolecular Systems , Max Planck Institute of Colloids and Interfaces , Am Mühlenberg 1 , 14424 Potsdam , Germany.
Institute of Chemistry and Biochemistry , Freie Universität Berlin , Arnimallee 22 , 14195 Berlin , Germany.
J Med Chem. 2018 Jun 14;61(11):4918-4927. doi: 10.1021/acs.jmedchem.8b00312. Epub 2018 May 18.
Fully synthetic glycan-based vaccines hold great potential as preventive and therapeutic vaccines against infectious diseases as well as cancer. Here, we present a two-component platform based on the facile conjugation of carbohydrate antigens to α-galactosylceramide (α-GalCer) to yield fully synthetic vaccine candidates. Formulation of the cancer-associated Tn antigen glycolipid model vaccine candidate into liposomes of different sizes and subsequent immunization of mice generated specific, high-affinity antibodies against the carbohydrate antigen with characteristics of T cell-dependent immunity. Liposome formulation elicited more reproducible glycan immunity than a conventional glycoconjugate vaccine bearing the same glycan antigen did. Further evaluation of the immune response revealed that the size of the liposomes influenced the glycan antibody responses toward either a cellular (Th1) or a humoral (Th2) immune phenotype. The glycolipid vaccine platform affords strong and robust antiglycan antibody responses in vivo without the need for an external adjuvant.
基于聚糖的全合成疫苗在预防和治疗传染病以及癌症方面具有巨大潜力。在这里，我们提出了一个基于简单地将碳水化合物抗原与α-半乳糖神经酰胺（α-GalCer）偶联的两部分平台，以产生全合成疫苗候选物。将癌症相关的 Tn 抗原糖脂模型疫苗候选物配制成不同大小的脂质体，随后对小鼠进行免疫接种，可产生针对碳水化合物抗原的特异性、高亲和力抗体，具有 T 细胞依赖性免疫的特征。与具有相同糖抗原的传统糖缀合物疫苗相比，脂质体配方可产生更具重现性的聚糖免疫。进一步评估免疫反应表明，脂质体的大小影响了针对细胞（Th1）或体液（Th2）免疫表型的聚糖抗体反应。该糖脂疫苗平台在体内产生强大而稳健的抗聚糖抗体反应，而无需外部佐剂。
