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Chimeric oligosaccharide conjugate induces opsonic antibodies against Streptococcus pneumoniae serotypes 19A and 19F
Chemical Science ( IF 8.4 ) Pub Date : 2020-06-26 , DOI: 10.1039/d0sc02230f
Someswara Rao Sanapala 1, 2, 3, 4 , Bruna M. S. Seco 1, 2, 3, 4, 5 , Ju Yuel Baek 1, 2, 3, 4 , Shahid I. Awan 1, 2, 3, 4 , Claney L. Pereira 4, 5, 6, 7 , Peter H. Seeberger 1, 2, 3, 4, 5
Affiliation  

Streptococcus pneumoniae 19A (ST19A) and 19F (ST19F) are among the prevalent serotypes causing pneumococcal disease worldwide even after introduction of a 13-valent pneumococcal conjugate vaccine (PCV13). Synthetic glycoconjugate vaccines have defined chemical structures rather than isolated polysaccharide mixtures utilized in marketed vaccines. Ideally, a minimal number of synthetic antigens would cover as many bacterial serotypes to lower cost of goods and minimize the response to carrier proteins. To demonstrate that a chimeric oligosaccharide antigen can induce a protective immune response against multiple serotypes, we synthesized a chimeric antigen (ST19AF) that is comprised of a repeating unit of ST19A and ST19F capsular polysaccharide each. Synthetic glycan epitopes representing only ST19A, and ST19F were prepared for comparison. Semisynthetic glycoconjugates containing chimeric antigen ST19AF induced high antibody titers able to recognize native CPS from ST19A and ST19F in rabbits. The antibodies were able to kill both strains of pneumococci. Chimeric antigens are an attractive means to induce an immune response against multiple bacterial serotypes.

中文翻译:

嵌合寡糖缀合物诱导抗肺炎链球菌血清型19A和19F的调理抗体

肺炎链球菌即使在引入13价肺炎球菌结合疫苗(PCV13)之后,19A(ST19A)和19F(ST19F)仍是导致全世界肺炎球菌疾病的流行血清型。合成糖缀合物疫苗具有确定的化学结构,而不是市售疫苗中使用的分离的多糖混合物。理想地,最少数量的合成抗原将覆盖尽可能多的细菌血清型,以降低商品成本并使对载体蛋白的反应降至最低。为了证明嵌合寡糖抗原可以诱导针对多种血清型的保护性免疫应答,我们合成了一种嵌合抗原(ST19AF),该抗原分别由ST19A和ST19F荚膜多糖的重复单元组成。制备仅代表ST19A和ST19F的合成聚糖表位用于比较。含有嵌合抗原ST19AF的半合成糖缀合物诱导了高抗体滴度,能够识别兔中来自ST19A和ST19F的天然CPS。抗体能够杀死两种肺炎球菌。嵌合抗原是诱导针对多种细菌血清型的免疫应答的有吸引力的手段。
更新日期:2020-07-22
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