PDF(Pubmed)
Abstract：
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.
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.
摘要：
背景：肺炎链球菌血清型3仍然是一个全球性的问题。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增。
方法：使用来自全球肺炎球菌测序项目的序列评估了血清型3全球肺炎球菌序列簇（GPSCs）和序列类型（STs）的分布。来自布兰太尔的135种血清型3运输分离株的全基因组序列，马拉维（2015-2019）进行了分析。胶囊轨迹的比较分析，整个基因组,抗菌素耐药性，并进行了系统发育重建。使用来自接种疫苗的成人和儿童的血清样品评估视细胞吞噬作用。
结果：血清型3GPSC10-ST700分离株在马拉维最为突出。与原型血清型3荚膜多糖基因座序列相比，6个基因缺失，保留胶囊多糖的生物合成。该谱系的特征在于增加的抗微生物抗性和较低的对调理吞噬杀伤的敏感性。
结论：马拉维的3型血清型变异体具有基因型和表型特征，可以在PCV13引入后增强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。
方法：使用来自全球肺炎球菌测序项目的序列评估了血清型3全球肺炎球菌序列簇（GPSCs）和序列类型（STs）的分布。来自布兰太尔的135种血清型3运输分离株的全基因组序列，马拉维（2015-2019）进行了分析。胶囊轨迹的比较分析，整个基因组,抗菌素耐药性，并进行了系统发育重建。使用来自接种疫苗的成人和儿童的血清样品评估视细胞吞噬作用。
结果：血清型3GPSC10-ST700分离株在马拉维最为突出。与原型血清型3荚膜多糖基因座序列相比，6个基因缺失，保留胶囊多糖的生物合成。该谱系的特征在于增加的抗微生物抗性和较低的对调理吞噬杀伤的敏感性。
结论：马拉维的3型血清型变异体具有基因型和表型特征，可以在PCV13引入后增强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。
