Sanapala Someswara Rao, Seco Bruna M S, Baek Ju Yuel, Awan Shahid I, Pereira Claney L, Seeberger Peter H
Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces Am Mūhlenberg 1 D-14424 Potsdam Germany
Department of Chemistry and Biochemistry, Freie Universität Berlin Arnimallee 22 D-14195 Berlin Germany.
Chem Sci. 2020 Jun 26;11(28):7401-7407. doi: 10.1039/d0sc02230f.
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 . Chimeric antigens are an attractive means to induce an immune response against multiple bacterial serotypes.
即使在引入13价肺炎球菌结合疫苗（PCV13）之后，19A（ST19A）和19F（ST19F）仍是全球范围内引起肺炎球菌疾病的常见血清型。合成糖缀合物疫苗具有明确的化学结构，而非市售疫苗中使用的分离多糖混合物。理想情况下，最少数量的合成抗原应能覆盖尽可能多的细菌血清型，以降低生产成本并尽量减少对载体蛋白的反应。为证明嵌合寡糖抗原可诱导针对多种血清型的保护性免疫反应，我们合成了一种嵌合抗原（ST19AF），其由ST19A和ST19F荚膜多糖的重复单元各一个组成。制备了仅代表ST19A和ST19F的合成聚糖表位用于比较。含有嵌合抗原ST19AF的半合成糖缀合物在兔体内诱导出了能够识别来自ST19A和ST19F的天然CPS的高抗体滴度。这些抗体能够杀死这两种菌株。嵌合抗原是诱导针对多种细菌血清型免疫反应的一种有吸引力的手段。
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