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

Akuzike Kalizang'oma; Todd D Swarthout; Thandie S Mwalukomo; Arox Kamng'ona; Comfort Brown; Jacquline Msefula; Hayley Demetriou; Jia Mun Chan; Lucy Roalfe; Uri Obolski; Jose Lourenço; David Goldblatt; Chrispin Chaguza; Neil French; Robert S Heyderman

doi:10.1093/infdis/jiae040

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

J Infect Dis. 2024 Mar 26:jiae040. doi: 10.1093/infdis/jiae040. Online ahead of print.

Authors

Akuzike Kalizang'oma^{1

2}, Todd D Swarthout^{1

2

3}, Thandie S Mwalukomo⁴, Arox Kamng'ona⁵, Comfort Brown², Jacquline Msefula², Hayley Demetriou⁶, Jia Mun Chan¹, Lucy Roalfe⁶, Uri Obolski⁷, Jose Lourenço⁸, David Goldblatt^{1

6}, Chrispin Chaguza^{1

9

10

11}, Neil French¹², Robert S Heyderman^{1

2}

Affiliations

¹ NIHR Mucosal Pathogens Research Unit, Research Department of Infection, Division of Infection and Immunity, University College London, London, United Kingdom.
² Pneumonia and Meningitis Pathogens Associate Research Group, Malawi-Liverpool-Wellcome Research Programme, Blantyre, Malawi.
³ Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.
⁴ School of Medicine and Oral Health, Kamuzu University of Health Sciences, Blantyre, Malawi.
⁵ School of Life Sciences and Allied Health Professionals, Kamuzu University of Health Sciences, Blantyre, Malawi.
⁶ Great Ormond Street Institute of Child Health, University College London, London, United Kingdom.
⁷ Porter School of the Environment and Earth Science, Tel-Aviv University, Tel-Aviv, Israel.
⁸ Faculdade de Ciências, BioISI, Universidade de Lisboa, Lisbon, Portugal.
⁹ Parasites and Microbes Programme, Wellcome Sanger Institute, Hinxton, United Kingdom.
¹⁰ Department of Epidemiology of Microbial Diseases, Yale School of Public Health, Yale University, New Haven, Connecticut, USA.
¹¹ Yale Institute for Global Health, Yale University, New Haven, Connecticut, USA.
¹² Institute of Infection, Veterinary and Ecological Sciences, Department of Clinical Infection, Microbiology and Immunology, University of Liverpool, Liverpool, United Kingdom.

PMID: 38530917
DOI: 10.1093/infdis/jiae040

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.

Keywords: Streptococcus pneumoniae; Africa; capsule; pneumococcal conjugate vaccine; serotype 3.