Pfizer Vaccine Research & Development, 401 N. Middletown Rd, Pearl River, NY 10965, USA.
Department of Computer Science, University of Cape Town, Rondebosch 7701, South Africa.
Vaccine. 2022 Aug 5;40(33):4872-4880. doi: 10.1016/j.vaccine.2022.06.041. Epub 2022 Jul 7.
Protection conferred by pneumococcal polysaccharide conjugate vaccines (PCVs) is associated with PCV-induced antibodies against vaccine-covered serotypes that exhibit functional opsonophagocytic activity (OPA). Structural similarity between capsular polysaccharides of closely related serotypes may result in induction of cross-reactive antibodies with or without a cross-functional activity against a serotype not covered by a PCV, with the former providing an additional protective clinical benefit. Serotypes 15B, 15A, and 15C, in the serogroup 15, are among the most prevalent Streptococcus pneumoniae serotypes associated with invasive pneumococcal disease following the implementation of a 13-valent PCV; in addition, 15B contributes significantly to acute otitis media. Serological discrimination between closely related serotypes such as 15B and 15C is complicated; here, we implemented an algorithm to quickly differentiate 15B from its closely related serotypes 15C and 15A directly from whole-genome sequencing data. In addition, molecular dynamics simulations of serotypes 15A, 15B, and 15C polysaccharides demonstrated that while 15B and 15C polysaccharides assume rigid branched conformation, 15A polysaccharide assumes a flexible linear conformation. A serotype 15B conjugate, included in a 20-valent PCV (PCV20), induced cross-functional OPA serum antibody responses against the structurally similar serotype 15C but not against serotype 15A, both not included in PCV20. In PCV20-vaccinated adults (18-49 years), robust OPA antibody titers were detected against both serotypes 15B (the geometric mean titer [GMT] of 19,334) and 15C (GMTs of 1692 and 2747 for strains PFE344340 and PFE1160, respectively), but were negligible against serotype 15A (GMTs of 10 and 30 for strains PFE593551 and PFE647449, respectively). Cross-functional 15B/C responses were also confirmed using sera from a larger group of older adults (60-64 years).
肺炎球菌多糖结合疫苗 (PCV) 提供的保护与 PCV 诱导的针对疫苗覆盖血清型的抗体有关，这些抗体具有功能性调理吞噬作用 (OPA)。密切相关血清型的荚膜多糖结构相似，可能导致产生针对 PCV 未覆盖血清型的交叉反应性抗体，具有或不具有交叉功能活性，前者提供额外的保护性临床益处。血清型 15B、15A 和 15C 属于血清群 15 中与 13 价 PCV 实施后侵袭性肺炎球菌病相关的最常见肺炎球菌血清型；此外，15B 对急性中耳炎有重要贡献。15B 和 15C 等密切相关血清型的血清学区分很复杂；在这里，我们实施了一种算法，可直接从全基因组测序数据中快速区分 15B 与其密切相关的血清型 15C 和 15A。此外，血清型 15A、15B 和 15C 多糖的分子动力学模拟表明，15B 和 15C 多糖呈现刚性分支构象，而 15A 多糖呈现灵活的线性构象。包含在 20 价 PCV (PCV20) 中的 15B 血清型结合物诱导针对结构相似的血清型 15C 的交叉功能 OPA 血清抗体反应，但不针对不在 PCV20 中的血清型 15A。在接种 PCV20 的成年人（18-49 岁）中，针对血清型 15B（PFE344340 株的几何平均滴度 [GMT] 为 19334）和 15C（PFE1160 株的 GMTs 分别为 1692 和 2747）均检测到强大的 OPA 抗体滴度，但针对血清型 15A 的滴度可忽略不计（PFE593551 株和 PFE647449 株的 GMTs 分别为 10 和 30）。使用来自更大年龄组成年人（60-64 岁）的血清也证实了交叉功能 15B/C 反应。
