Poster Presentation Australian Society for Microbiology Annual Scientific Meeting 2023

Effect of childhood vaccination on the pneumococcal population in Mongolia (#191)

Paige Skoko 1 , Laura Boelsen 1 , Sam Manna 1 , Stephanie Lo 2 , Casey Pell 1 , Belinda Ortika 1 , Kim Mulholland 3 4 5 , Tuya Mungun 6 , Claire von Mollendorf 3 , Stephen Bentley 2 , Catherine Satzke 1 4 7
  1. Translational Microbiology, Murdoch Children's Research Institute, Parkville, Australia
  2. Parasites and Microbes, Wellcome Trust Sanger Institute, Hinxton, United Kingdom
  3. New Vaccines, Murdoch Children’s Research Institute, Parkville, Australia
  4. Department of Paediatrics, The University of Melbourne, Parkville, Australia
  5. Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom
  6. National Centre for Communicable Diseases, Ministry of Health, Ulaanbaatar, Mongolia
  7. Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, Australia

Streptococcus pneumoniae (the pneumococcus) is the leading cause of pneumonia in children under five years of age. Pneumococcal conjugate vaccines (PCVs) target a subset of serotypes. PCVs are effective at reducing disease, however, some vaccine-types persist, and over time serotype replacement occurs.

Mongolia introduced PCV in 2016 with catch-up. To measure the effect of vaccine introduction, we established a comprehensive active surveillance program (2015-2021), collecting n=15,183 nasopharyngeal swabs from children with pneumonia across four Mongolian districts. Previously, swabs (n=6,651) were screened for pneumococci and DNA microarray was performed to infer serotype. Several non-vaccine serotypes (15A, 15B/C and 10A) have become important replacers, whilst some vaccine serotypes (6A, 6B, 19F and 23F) persisted and remain a likely cause of pneumonia in Mongolian children.

We aim to investigate serotype persistence following vaccine introduction in Mongolia. Using DNA microarray data, we inferred genetic lineage (characterised by Global Pneumococcal Sequence Cluster, GPSC) and examined lineage changes post-PCV. There was evidence of lineage replacement among vaccine-serotype 6B, where the dominant lineage pre-PCV was GPSC23 (76%), which was replaced by GPSC6 post-PCV (83%), P<0.0001, Fisher’s exact test.

To understand the biological differences between lineages GPSC23 and GPSC6 that could explain this lineage replacement, we used an infant mouse model. Infant mice (five days old) were infected intranasally with GPSC23 or GPSC6 (one isolate per lineage). GPSC23 colonised to a higher pneumococcal density in the nasopharynx at seven days post-infection (P=0.03, Mann-Whitney). GPSC23 disseminated to the lungs and blood and was more virulent (86% moribund) than GPSC6 (14% moribund at 20 days of age), P<0.0001, Mantel-Cox test. 

Next, we sequenced 10 GPSC23 and 7 GPSC6 isolates on the NovaSeq 6000 (Illumina) platform. Comparative genomics was conducted using Roary, identifying 13 genes that differ between the two lineages that may contribute to differences in virulence which will be further investigated.

Overall we found that the GPSC6 lineage is less virulent, likely translating to fewer deaths attributable to serotype 6B post-PCV. Ultimately, this finding adds confidence to the vaccine program in Mongolia. Future experiments will examine other phenotypes such as vaccine escape to better understand lineage emergence.