A semisynthetic carbohydrate-lipid vaccine that protects against S-pneumoniae in mice
A semisynthetic carbohydrate-lipid vaccine that protects against S-pneumoniae in mice
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DOI：
10.1038/nchembio.1650
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发表时间：
2014-11-01
影响因子：
14.8
通讯作者：
De Libero, Gennaro
中科院分区：
文献类型：
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作者：
Cavallari, Marco;Stallforth, Pierre;De Libero, Gennaro
尽管广泛采用了针对肺炎链球菌的碳水化合物-蛋白质结合疫苗，但严重形式的肺炎球菌脑膜炎、菌血症和肺炎每年仍导致超过 100 万人死亡。在这里，我们描述了一种新的高效抗肺炎球菌疫苗设计，其基于肺炎链球菌荚膜多糖与强效脂质抗原α-半乳糖神经酰胺的合成缀合，当由非多态性抗原呈递分子CD1d呈递时，它会刺激不变的自然杀伤T（iNKT）细胞。注射新型脂质-碳水化合物结合疫苗的小鼠产生了针对肺炎球菌多糖的高亲和力 IgG 抗体。疫苗接种刺激生发中心形成；具有滤泡辅助性 T 细胞表型的 iNKT 细胞的积累；碳水化合物特异性、长寿命记忆 B 细胞和浆母细胞的频率增加。这种新的脂质-碳水化合物疫苗接种策略诱导了有效的抗多糖免疫，可以保护小鼠免受肺炎球菌疾病的侵害，并且也可能被证明对于设计针对其他主要细菌病原体的基于碳水化合物的疫苗是有效的。
Severe forms of pneumococcal meningitis, bacteraemia and pneumonia result in more than 1 million deaths each year despite the widespread introduction of carbohydrate-protein conjugate vaccines against Streptococcus pneumoniae. Here we describe a new and highly efficient antipneumococcal vaccine design based on synthetic conjugation of S. pneumoniae capsule polysaccharides to the potent lipid antigen alpha-galactosylceramide, which stimulates invariant natural killer T (iNKT) cells when presented by the nonpolymorphic antigen-presenting molecule CD1d. Mice injected with the new lipid-carbohydrate conjugate vaccine produced high-affinity IgG antibodies specific for pneumococcal polysaccharides. Vaccination stimulated germinal center formation; accumulation of iNKT cells with a T follicular helper cell phenotype; and increased frequency of carbohydrate-specific, long-lived memory B cells and plasmablasts. This new lipid-carbohydrate vaccination strategy induced potent antipolysaccharide immunity that protected against pneumococcal disease in mice and may also prove effective for the design of carbohydrate-based vaccines against other major bacterial pathogens.