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Synthesis, Liposomal Formulation, and Immunological Evaluation of a Minimalistic Carbohydrate-α-GalCer Vaccine Candidate
Journal of Medicinal Chemistry ( IF 7.3 ) Pub Date : 2018-05-09 00:00:00 , DOI: 10.1021/acs.jmedchem.8b00312
Felix Broecker 1, 2 , Sebastian Götze 1, 2 , Jonathan Hudon 1 , Dominea C. K. Rathwell 1 , Claney L. Pereira 1 , Pierre Stallforth 1 , Chakkumkal Anish 1 , Peter H. Seeberger 1, 2
Affiliation  

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.

中文翻译:

碳水化合物-α-GalCer候选疫苗的合成,脂质体制剂和免疫学评价

完全基于合成聚糖的疫苗具有巨大的潜力,可作为针对传染病和癌症的预防和治疗疫苗。在这里,我们提出了一个基于碳水化合物抗原与α-半乳糖基神经酰胺(α-GalCer)结合的两组分平台,以产生完全合成的疫苗候选物。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,然后对小鼠进行免疫,从而产生针对碳水化合物抗原的具有T细胞依赖性免疫特性的特异性,高亲和力抗体。与携带相同聚糖抗原的常规糖缀合物疫苗相比,脂质体制剂可产生更高的可重复聚糖免疫力。对免疫反应的进一步评估表明,脂质体的大小影响了聚糖对细胞(Th1)或体液(Th2)免疫表型的反应。糖脂疫苗平台可提供强大而强大的抗聚糖抗体反应体内不需要外部佐剂。
更新日期:2018-05-09
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