Streptococcus pneumoniae (the pneumococcus) is a leading cause of death for children under five years of age. Colonisation of the nasopharynx by the pneumococcus is usually asymptomatic, however, the pneumococcus can disseminate to other anatomic sites to cause diseases such as otitis media, pneumonia, sepsis and meningitis. Pneumococcal conjugate vaccines (PCVs), targeting a subset of pneumococcal capsular types (serotypes), are effective at reducing the disease burden. However, some vaccine-serotypes persist, a phenomenon that is poorly understood, particularly in Asia. Here, we investigate vaccine-serotype persistence post-PCV introduction in Mongolia.
Hospital-based pneumonia surveillance (2015-2021) was conducted across four Mongolian districts to measure the effect of vaccine introduction in 2016. Nasopharyngeal swabs (n=15,183) were collected from children with pneumonia and a subset (n=6,545) were screened for pneumococci and serotyped using DNA microarray. To understand the genetic background of circulating serotypes, we used DNA microarray to infer genetic lineage (using Global Pneumococcal Sequence Cluster, GPSC) and examined lineage changes post-PCV. Using an infant mouse model of disease, we explored differences in colonisation and disease dynamics between lineages, by infecting C57BL/6 mice (five days old) intranasally with pneumococci, testing three isolates per lineage to date.
Overall, vaccine-serotype prevalence reduced post-PCV introduction. However, some individual vaccine-serotypes (6A, 6B, 19F and 23F) persisted and remain a likely cause of pneumonia. Within serotype 6B, GPSC23 was the dominant lineage pre-PCV (16/21, 76% in 2015), which was replaced by GPSC6 (15/18, 83% in 2020) post-PCV, p<0.0001. In our mouse model, GPSC23 colonised to a higher pneumococcal density in the nasopharynx than GPSC6 (p=0.037) at seven days post-infection. GPSC23 had a higher tendency to transition to disease, with 92% (22/24) of mice becoming moribund compared with 7% (2/28) in the GPSC6 lineage (p<0.0001). Tissues were collected from 18 moribund mice, finding GPSC23 had disseminated throughout the body including to the lungs (n=14), blood (n=13), brain (n=13) and middle ear (n=13).
Despite persistence of vaccine-serotype 6B, our data indicates that a lineage replacement occurred, and the emerging lineage may be less virulent. Future experiments will examine the process of lineage replacement and the genetic differences between lineage.