Streptococcus pneumoniae vaccine serotype persistence following 13-valent pneumococcal conjugate vaccine introduction in Mongolia: investigating changes in epidemiology, immunology and virulence
BackgroundStreptococcus pneumoniae is a leading cause of pneumonia globally. Vaccine serotypes can persist despite pneumococcal conjugate vaccine (PCV) introduction. To examine serotype persistence, we leveraged 6,545 nasopharyngeal swabs collected from children hospitalised with pneumonia before and after PCV13 introduction in Mongolia and undertook molecular, epidemiological and experimental analyses. MethodsSerotype, genetic lineage and antimicrobial resistance genes were inferred from DNA microarray. Patients carrying lineages that were predominant pre- and post-PCV introduction were examined for differences in disease severity. We also compared the pre- and post-PCV lineages by bacterial adhesion to hydrocarbon (BATH) and enzyme-linked immunosorbent (ELISA) assays. Capsule gene expression was measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR), capsule thickness by transmission electron microscopy, and virulence using an infant mouse model. FindingsChanges in lineage composition were observed within serotypes 6A, 6B, 14, 19F and 23F over the six-year surveillance period. Children carrying pre-PCV lineages were more likely to have severe pneumonia than those carrying post-PCV lineages (serotypes 6B, 14 and 19F). Pre-PCV lineages were more likely to be multi-drug resistant than post-PCV lineages (serotypes 6A, 6B and 23F). For serotype 6B the post-PCV lineage had higher cell surface hydrophobicity, lower IgG, lower expression of capsule genes and evidence of thinner capsule than the pre-PCV lineage. Notably, the post-PCV 6B lineage was also less virulent in mice than the pre-PCV 6B lineage. InterpretationDespite persistence of vaccine serotypes in highly vaccinated populations, vaccination may select for lineages with differences in capsule and antibody binding and that are less virulent. When evaluating the true value of vaccination, it is important to consider factors beyond serotype alone. FundingNational Health and Medical Research Council, Murdoch Childrens Research Institute, GAVI, the Vaccine Alliance.