{Reference Type}: Journal Article
{Title}: Clonal Expansion of a Streptococcus pneumoniae Serotype 3 Capsule Variant Sequence Type 700 With Enhanced Vaccine Escape Potential After 13-Valent Pneumococcal Conjugate Vaccine Introduction.
{Author}: Kalizang'oma A;Swarthout TD;Mwalukomo TS;Kamng'ona A;Brown C;Msefula J;Demetriou H;Chan JM;Roalfe L;Obolski U;Lourenço J;Goldblatt D;Chaguza C;French N;Heyderman RS;
{Journal}: J Infect Dis
{Volume}: 230
{Issue}: 1
{Year}: 2024 Jul 25
{Factor}: 7.759
{DOI}: 10.1093/infdis/jiae040
{Abstract}: <B>BACKGROUND: </B>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.<BR><B>METHODS: </B>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.<BR><B>RESULTS: </B>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.<BR><B>CONCLUSIONS: </B>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.