DTaP and toxins division, National Institutes for Food and Drug Control, Key Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products, Beijing, China.
PLoS One. 2019 Jul 10;14(7):e0218427. doi: 10.1371/journal.pone.0218427. eCollection 2019.
This study aimed to explore the feasibility of pneumococcal surface protein A (PspA) as a carrier protein. Three recombinant pneumococcal surface proteins from three different clades were expressed by the prokaryotic expression system and conjugated to group A meningococcal polysaccharide (GAMP) to generate three polysaccharide-protein conjugates. The conjugates, unconjugated proteins, GAMP, and GAMP-TT vaccine bulk (used as positive control) were immunized into mice, and their immune effects were assessed by the methods of enzyme-linked immunosorbent assay (ELISA), flow cytometry (FCM), and serum bactericidal assay (SBA). The results showed that the polysaccharide-protein conjugates could produce higher levels of anti-GAMP IgG titers (P < 0.05), higher ratios of Th1/Th2 (P < 0.05), and higher levels of serum bactericidal activity (P < 0.05), compared with the unconjugated GAMP. The conjugation of PspAs to GAMP also enhanced the anti-PspA responses compared with unconjugated PspAs except for PspA3. In conclusion, the results indicated that the three PspAs were appropriate carrier proteins, as demonstrated by the characteristics of T-cell dependent responses to the GAMP, and might protect against group A of epidemic cerebrospinal meningitis.
本研究旨在探索肺炎球菌表面蛋白 A (PspA) 作为载体蛋白的可行性。通过原核表达系统表达了来自三个不同进化枝的三种重组肺炎球菌表面蛋白，并将其与 A 群脑膜炎球菌多糖 (GAMP) 缀合，生成三种多糖-蛋白缀合物。将缀合物、未缀合的蛋白、GAMP 和 GAMP-TT 疫苗粗品（用作阳性对照）免疫小鼠，通过酶联免疫吸附试验 (ELISA)、流式细胞术 (FCM) 和血清杀菌试验 (SBA) 评估其免疫效果。结果表明，与未缀合的 GAMP 相比，多糖-蛋白缀合物能产生更高水平的抗 GAMP IgG 效价（P < 0.05）、更高的 Th1/Th2 比值（P < 0.05）和更高水平的血清杀菌活性（P < 0.05）。与未缀合的 PspA 相比，除 PspA3 外，PspA 与 GAMP 的缀合也增强了抗 PspA 反应。总之，结果表明，这三种 PspA 是合适的载体蛋白，具有依赖于 T 细胞的 GAMP 反应的特征，可能对 A 群流行性脑脊髓膜炎具有保护作用。
