Synthesis, Liposomal Formulation, and Immunological Evaluation of a Minimalistic Carbohydrate-α-GalCer Vaccine Candidate
Synthesis, Liposomal Formulation, and Immunological Evaluation of a Minimalistic Carbohydrate-α-GalCer Vaccine Candidate
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DOI：
10.1021/acs.jmedchem.8b00312
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发表时间：
2018-06-14
影响因子：
7.3
通讯作者：
Seeberger, Peter H.
中科院分区：
文献类型：
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作者：
Broecker, Felix;Goetze, Sebastian;Seeberger, Peter H.
全合成聚糖疫苗作为传染病和癌症的预防和治疗疫苗具有巨大的潜力。在这里，我们提出了一个基于碳水化合物抗原与α-半乳糖神经酰胺（α-GalCer）轻松缀合的双组分平台，以产生完全合成的候选疫苗。将癌症相关 Tn 抗原糖脂模型疫苗候选物配制为不同大小的脂质体，随后对小鼠进行免疫，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。与具有相同聚糖抗原的传统糖复合物疫苗相比，脂质体制剂引发了更可重复的聚糖免疫。对免疫反应的进一步评估表明，脂质体的大小影响聚糖抗体对细胞（Th1）或体液（Th2）免疫表型的反应。糖脂疫苗平台无需外部佐剂即可在体内提供强大的抗聚糖抗体反应。
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 a-galactosylceramide (alpha-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.