Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing 100071, China.
State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China.
Mediators Inflamm. 2020 Jul 4;2020:9596129. doi: 10.1155/2020/9596129. eCollection 2020.
The encapsulated bacteria, as , type b, and , cause serious morbidity and mortality worldwide. The capsular polysaccharide (PS), which could elicit a weak T cell-independent immune response, is a vital virulence determinant. One of the strategies to improve the PS-specific immunogenicity is to conjugate PS with a nontoxic carrier protein. Tetanus toxoid (TT) and CRM are the typical carrier proteins for the PS conjugate vaccines. TT is the inactivated tetanus toxin manipulated with formaldehyde, which suffers from the pollution from residual formaldehyde and the incomplete detoxification. CRM has the disadvantage of low-yield purification with the requirement of sophisticated culture conditions. Thus, a novel carrier protein without these disadvantages is highly required. The tetanus toxin native C-fragment (Hc) is safe, low-cost, and highly immunogenic with easy purification, which can act as a promising carrier protein. Pneumococcal serogroups 14 and 23F were major epidemic causes of pneumococcal infections. In the present study, the capsular PSs (PS14 and PS23F) were conjugated with Hc, TT, and CRM, respectively. TT- and CRM-based conjugates acted as controls for Hc-based conjugates (PS14-Hc and PS23F-Hc). The structural properties of Hc were not fundamentally changed after conjugated with PS. PS14-Hc and PS23F-Hc could potentiate sound PS-specific antibody levels comparable to the controls. Thus, Hc exhibited a practical carrier effect to help the pneumococcal conjugate vaccines perform good immunogenicities.
encapsulated 细菌，如 type b ， 和 ，在全球范围内导致严重的发病率和死亡率。荚膜多糖 (PS) ，它可以引起较弱的 T 细胞非依赖性免疫反应，是一个重要的毒力决定因素。提高 PS 特异性免疫原性的策略之一是将 PS 与无毒载体蛋白结合。破伤风类毒素 (TT) 和 CRM 是 PS 结合疫苗的典型载体蛋白。TT 是用甲醛处理的失活破伤风毒素，存在残留甲醛污染和不完全解毒的问题。CRM 的缺点是产量低，纯化要求复杂的培养条件。因此，非常需要一种没有这些缺点的新型载体蛋白。破伤风毒素天然 C 片段 (Hc) 安全、低成本、免疫原性高，易于纯化，可以作为一种有前途的载体蛋白。肺炎球菌血清型 14 和 23F 是肺炎球菌感染的主要流行原因。在本研究中，分别将荚膜 PS (PS14 和 PS23F) 与 Hc、TT 和 CRM 结合。TT 和 CRM 基缀合物作为 Hc 基缀合物 (PS14-Hc 和 PS23F-Hc) 的对照。PS 结合后 Hc 的结构特性没有根本改变。PS14-Hc 和 PS23F-Hc 可以增强与对照相当的良好 PS 特异性抗体水平。因此，Hc 表现出实际的载体效应，有助于肺炎球菌结合疫苗产生良好的免疫原性。
