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

• Published in: The Journal of infectious diseases Vol. 230; no. 1; pp. e189 - e198
• Main Authors: Kalizang'oma, Akuzike, Swarthout, Todd D, Mwalukomo, Thandie S, Kamng'ona, Arox, Brown, Comfort, Msefula, Jacquline, Demetriou, Hayley, Chan, Jia Mun, Roalfe, Lucy, Obolski, Uri, Lourenço, Jose, Goldblatt, David, Chaguza, Chrispin, French, Neil, Heyderman, Robert S
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 26.03.2024
• Subjects: Major; capsule; serotype 3; Africa; Streptococcus pneumoniae; pneumococcal conjugate vaccine
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1093/infdis/jiae040

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. 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. 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. 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.