Background Streptococcus pneumoniae serotype 3 remains a problem globally. Malawi introduced 13-valent pneumococcal conjugate vaccine (PCV13) in 2011, but there has been no direct protection against serotype 3 carriage. We explored whether vaccine escape by serotype 3 is due to clonal expansion of a lineage with a competitive advantage. Methods The distribution of serotype 3 Global Pneumococcal Sequence Clusters (GPSCs) and sequence types (STs) globally was assessed using sequences from the Global Pneumococcal Sequencing Project. Whole-genome sequences of 135 serotype 3 carriage isolates from Blantyre, Malawi (2015–2019) were analyzed. Comparative analysis of the capsule locus, entire genomes, antimicrobial resistance, and phylogenetic reconstructions were undertaken. Opsonophagocytosis was evaluated using serum samples from vaccinated adults and children. Results Serotype 3 GPSC10-ST700 isolates were most prominent in Malawi. Compared with the prototypical serotype 3 capsular polysaccharide locus sequence, 6 genes are absent, with retention of capsule polysaccharide biosynthesis. This lineage is characterized by increased antimicrobial resistance and lower susceptibility to opsonophagocytic killing. Conclusions A serotype 3 variant in Malawi has genotypic and phenotypic characteristics that could enhance vaccine escape and clonal expansion after post-PCV13 introduction. Genomic surveillance among high-burden populations is essential to improve the effectiveness of next-generation pneumococcal vaccines.

中文翻译：

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肺炎链球菌血清型 3 胶囊变体序列 700 型的克隆扩增，在 13 价肺炎球菌结合疫苗引入后具有增强的疫苗逃逸潜力

背景 肺炎链球菌血清型 3 仍然是一个全球性问题。马拉维于 2011 年推出了 13 价肺炎球菌结合疫苗 (PCV13)，但没有针对血清型 3 携带的直接保护。我们探讨了血清型 3 的疫苗逃逸是否是由于具有竞争优势的谱系的克隆扩张所致。方法 使用全球肺炎球菌测序项目的序列评估血清型 3 全球肺炎球菌序列簇 (GPSC) 和序列类型 (ST) 的全球分布。对来自马拉维布兰太尔（2015-2019）的 135 个血清型 3 携带分离株的全基因组序列进行了分析。对荚膜基因座、整个基因组、抗菌素耐药性和系统发育重建进行了比较分析。使用来自接种疫苗的成人和儿童的血清样本评估调理吞噬作用。结果 血清型 3 GPSC10-ST700 分离株在马拉维最为突出。与典型血清型3荚膜多糖基因座序列相比，缺少6个基因，保留了荚膜多糖生物合成。该谱系的特点是抗菌素耐药性增加和对调理吞噬细胞杀伤的敏感性较低。结论 马拉维的血清型 3 变种具有基因型和表型特征，可增强 PCV13 引入后的疫苗逃逸和克隆扩增。高负担人群的基因组监测对于提高下一代肺炎球菌疫苗的有效性至关重要。