PDF(Pubmed)
Abstract：
Serotypes 6C and 6D of Streptococcus pneumoniae are two major variants that cause invasive pneumococcal disease (IPD) in serogroup 6 alongside serotypes 6A and 6B. Since the introduction of the pneumococcal conjugate vaccines PCV7 and PCV13, the number of cases of IPD caused by pneumococcus in children and the elderly population has greatly decreased. However, with the widespread use of vaccines, a replacement effect has recently been observed among different serotypes and lowered the effectiveness of the vaccines. To investigate protection against the original serotypes and to explore protection against variants and replacement serotypes, we created a library of oligosaccharide fragments derived from the repeating units of the capsular polysaccharides of serotypes 6A, 6B, 6C, and 6D through chemical synthesis. The library includes nine pseudosaccharides with or without exposed terminal phosphate groups and four pseudotetrasaccharides bridged by phosphate groups. Six carbohydrate antigens related to 6C and 6D were prepared as glycoprotein vaccines for immunogenicity studies. Two 6A and two 6B glycoconjugate vaccines from previous studies were included in immunogenicity studies. We found that the conjugates containing four phosphate-bridged pseudotetrasaccharides were able to induce good immune antibodies and cross-immunogenicity by showing superior activity and broad cross-protective activity in OPKA bactericidal experiments.
摘要：
肺炎链球菌的血清型6C和6D是在血清群6中与血清型6A和6B一起引起侵袭性肺炎球菌疾病(IPD)的两种主要变体。自从引入肺炎球菌结合疫苗PCV7和PCV13以来，儿童和老年人群中由肺炎球菌引起的IPD的病例数大大减少。然而,随着疫苗的广泛使用，最近在不同血清型中观察到替代效应，并降低了疫苗的有效性。为了研究针对原始血清型的保护，并探索针对变体和替代血清型的保护，我们创建了一个来自血清型6A荚膜多糖重复单元的寡糖片段库，6B,6C,和6D通过化学合成。该文库包括9种具有或不具有暴露的末端磷酸基团的假糖和4种通过磷酸基团桥接的假四糖。制备了与6C和6D相关的六种碳水化合物抗原作为用于免疫原性研究的糖蛋白疫苗。来自先前研究的两种6A和两种6B糖缀合物疫苗包括在免疫原性研究中。我们发现，通过在OPKA杀菌实验中表现出优异的活性和广泛的交叉保护活性，含有四种磷酸桥联假四糖的缀合物能够诱导良好的免疫抗体和交叉免疫原性。
