The effects of pneumococcal conjugated vaccines (PCVs) need to be investigated. In Stockholm County, Sweden, PCV7 was introduced in the childhood immunisation programme in 2007 and changed to PCV13 in 2010.Over 90% of all invasive isolates during 2005–2014 (n=2336) and carriage isolates, 260 before and 647 after vaccine introduction, were characterised by serotyping, molecular typing and antibiotic susceptibility, and serotype diversity was calculated. Clinical information was collected for children and adults with invasive pneumococcal disease (IPD).The IPD incidence decreased post-PCV7, but not post-PCV13, in vaccinated children. Beneficial herd effects were seen in older children and adults, but not in the elderly. The herd protection was more pronounced post-PCV7 than post-PCV13. PCV7 serotypes decreased. IPD caused by PCV13 serotypes 3 and 19A increased post-PCV7. Post-PCV13, serotypes 6A and 19A, but not serotype 3, decreased. The serotype distribution changed in carriage and IPD to nonvaccine types, also in nonvaccinated populations. Expansion of non-PCV13 serotypes was largest following PCV13 introduction. Serotype diversity increased and nonvaccine clones emerged, such as CC433 (serotype 22F) in IPD and CC62 (serotype 11A) in carriage. In young children, meningitis, septicaemia and severe rhinosinusitis, but not bacteraemic pneumonia, decreased.Pneumococcal vaccination leads to expansion of new or minor serotypes/clones, also in nonvaccinated populations.

Pneumococccal conjugated pneumococcal vaccine (PCV10) and pneumococcal conjugate vaccine 13 (PCV13), are used in childhood immunization programs worldwide, but direct comparisons of impacts against invasive pneumococcal disease (IPD) in equivalent populations have not been performed. We compared the vaccines (prevaccination 2007–2009 vs postvaccination 2013–2016) in Sweden, where the 21 counties use either PCV10 or PCV13 (introduced 2009–2010). All IPD episodes (n = 16992) were recorded in Sweden during 2005–2016. Of 14186 from 2007–2016, 13468 (94.9%) were characterized with serotyping and 12235 (86.2%) with antibiotic susceptibility. Poisson models assessed changes in incidence over time. Invasive pneumococcal disease incidences decreased between 2005 and 2016 in vaccinated children (by 68.5%), and in the whole population (by 13.5%), but not among the elderly (increased by 2%), due to a substantial increase of non-vaccine types (NVTs). In 2016, NVTs constituted 72% of IPD cases in the elderly. Serotype 6A declined in PCV10 and PCV13 counties, whereas serotype 19A increased in PCV10 counties. There was no effect against serotype 3. Cross-protection was found between 6B and 6A, but not between 19F and 19A. Serotype 6C increased in PCV10 counties, but not in PCV13 counties, suggesting cross-protection with 6A, which is included in PCV13. In the elderly, the increase of NVTs excluding 6C, was more pronounced in PCV13 counties. The overall impact of IPD incidences was not statistically different irrespective of vaccine used. The incidence of serotypes, where the effect of the vaccines differed, will influence the cost-effectiveness of which vaccine to use in immunization programs. The dominance of NVTs suggests a limited effect of current pediatric PCVs against IPD in the elderly.

Streptococcus pneumoniae (the pneumococcus) is a human respiratory tract pathogen and a major cause of morbidity and mortality globally. Although the pneumococcus is a commensal bacterium that colonizes the nasopharynx, it also causes lethal diseases such as meningitis, sepsis, and pneumonia, especially in immunocompromised patients, in the elderly, and in young children. Due to the acquisition of antibiotic resistance and the emergence of nonvaccine serotypes, the pneumococcus has been classified as one of the priority pathogens for which new antibacterials are urgently required by the World Health Organization, 2017. Understanding molecular mechanisms behind the pathogenesis of pneumococcal infections and bacterial interactions within the host is crucial to developing novel therapeutics. Previously considered to be an extracellular pathogen, it is becoming evident that pneumococci may also occasionally establish intracellular niches within the body to escape immune surveillance and spread within the host. Intracellular survival within host cells also enables pneumococci to resist many antibiotics. Within the host cell, the bacteria exist in unique vacuoles, thereby avoiding degradation by the acidic lysosomes, and modulate the expression of its virulence genes to adapt to the intracellular environment. To invade and survive intracellularly, the pneumococcus utilizes a combination of virulence factors such as pneumolysin (PLY), pneumococcal surface protein A (PspA), pneumococcal adhesion and virulence protein B (PavB), the pilus-1 adhesin RrgA, pyruvate oxidase (SpxB), and metalloprotease (ZmpB). In this review, we discuss recent findings showing the intracellular persistence of Streptococcus pneumoniae and its underlying mechanisms.

Streptococcus pneumoniae is the main cause of bacterial meningitis, a life-threating disease with a high case fatality rate despite treatment with antibiotics. Pneumococci cause meningitis by invading the blood and penetrating the blood–brain barrier (BBB). Using stimulated emission depletion (STED) super-resolution microscopy of brain biopsies from patients who died of pneumococcal meningitis, we observe that pneumococci colocalize with the two BBB endothelial receptors: polymeric immunoglobulin receptor (pIgR) and platelet endothelial cell adhesion molecule (PECAM-1). We show that the major adhesin of the pneumococcal pilus-1, RrgA, binds both receptors, whereas the choline binding protein PspC binds, but to a lower extent, only pIgR. Using a bacteremia-derived meningitis model and mutant mice, as well as antibodies against the two receptors, we prevent pneumococcal entry into the brain and meningitis development. By adding antibodies to antibiotic (ceftriaxone)-treated mice, we further reduce the bacterial burden in the brain. Our data suggest that inhibition of pIgR and PECAM-1 has the potential to prevent pneumococcal meningitis.