Streptococcus pneumoniae genomic stability during human experimental colonization and vaccination

Streptococcus pneumoniae (Spn) infections are preceded by nasal colonization. By conferring protection against nasopharyngeal carriage, pneumococcal conjugate vaccines have reduced the global incidence of disease. Our understanding of vaccine-induced mechanisms of protection is aided by the Experimental Human Pneumococcal Challenge (EHPC) model, where healthy adult volunteers receive live Spn nasal inoculation. Here we evaluated the accumulation of Spn genetic diversity in the context of 13-valent pneumococcal conjugate vaccine (PCV13) immunization.

We compared single nucleotide polymorphisms (SNPs), insertions/deletions (INDELs), and pangenome elements in Spn strains isolated from EHPC participants who received PCV13 (n=5) to those who received the control hepatitis A vaccine (n=10). This required whole genome sequencing the 45 Spn strains spanning nasal wash samples that occurred at days 2, 7, 14 and 21/22 post-vaccination and the serotype 6B Spn inoculum.

There was no difference in number of variants or genome size over time between Spn strains from the PCV13 and control groups. The most prevalent genetic variants were identified in both groups and the PCV13 group accessory genome content was inclusive of that of the control. Across arms, variance in pangenome elements largely related to transposons.

While genomic variation was observed between the groups, mutations or acquisition of genes directly related to pathogenesis was not associated with exposure to PCV13 over the course of the study period. This suggests that PCV13 does not drive short-term selection for vaccine-escape during colonization, but longer-term studies are needed to assess potential delayed effects or impact on non-vaccine serotypes.