A peptide-free, liposome-based oligosaccharide vaccine, adjuvanted with a natural killer T cell antigen, generates robust antibody responses in vivo.
A peptide-free, liposome-based oligosaccharide vaccine, adjuvanted with a natural killer T cell antigen, generates robust antibody responses in vivo.
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DOI：
10.1039/c3sc53471e
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发表时间：
2014-04
期刊：
影响因子：
8.4
通讯作者：
Savage PB
中科院分区：
文献类型：
--
作者：
Deng S;Bai L;Reboulet R;Matthew R;Engler DA;Teyton L;Bendelac A;Savage PB
由于病原生物表面普遍存在低聚糖和多糖，碳水化合物是高等生物免疫系统产生的抗体识别的主要目标。因此，在开发基于碳水化合物表位的疫苗方面已经花费了大量的努力。典型的方法涉及在抗原肽或蛋白质上多价呈递碳水化合物靶标，这通常涉及大量的合成承诺和/或疫苗，其是异质的并且难以表征。我们已经开发了一种简单的基于脂质体的方法来产生多价碳水化合物疫苗，并且代替抗原肽或蛋白质，我们已经使用了针对自然杀伤T细胞的有效抗原。该疫苗基于肺炎链球菌血清型14多糖，其应答上级于临床使用的疫苗（Prevnar）。通过与寡糖和自然杀伤T细胞佐剂的简单混合物进行比较，证明了这种响应对脂质体形成的依赖性。通过使用有效的合成佐剂和较弱的细菌衍生的糖脂佐剂观察佐剂强度的重要性。这些结果证明了这种新的和相对简单的产生基于碳水化合物的疫苗的方法的有效性。
Due to the prevalence of oligo- and polysaccharides on the surfaces of pathogenic organisms, carbohydrates are primary targets for recognition by antibodies generated by the immune systems of higher organisms. Consequently, substantial effort has been expended in efforts to develop vaccines based on carbohydrate epitopes. Typical approaches involve multivalent presentation of carbohydrate targets on antigenic peptides or proteins, which often involve substantial synthetic commitments and/or vaccines that are heterogeneous and difficult to characterize. We have developed a simple, liposome-based approach to generate multivalent carbohydrate vaccines, and in place of an antigenic peptide or protein, we have used a potent antigen for natural killer T cells. This vaccine, based on the Streptococcus pneumoniae serotype 14 polysaccharide, gave a response superior to that from a clinically used vaccine (Prevnar). The dependence of this response on liposome formation was demonstrated by comparison to a simple mixture of the oligosaccharide and the natural killer T cell adjuvant. The importance of the strength of the adjuvant was observed by use of a potent synthetic adjuvant and a weaker, bacterial derived glycolipid adjuvant. These results demonstrate the effectiveness of this novel and relatively simple means of generating carbohydrate-based vaccines.