Defining the protein-based protective immune mechanisms to Streptococcus pneumoniae throughout life
Streptococcus pneumoniae is a Gram positive bacteria that primarily resides as a commensal in the human nasopharynx of children < 5 years old. Aside from being commensal, S. pneumoniae is also the leading cause of community-acquired pneumonia and capable of causing invasive diseases such as bacteraemia and meningitis.
Episodes of pneumococcal colonization and exposure throughout life allow the host to acquire and build up an efficient natural acquired immunity against the bacteria, consisting of immune responses specific for the outer layer of capsular polysaccharides and the pneumococcal proteins.
Despite this, children and older adults remain highly susceptible for invasive pneumococcal diseases (IPD). Therefore, pneumococcal vaccines PCV (Polysaccharide Conjugate Vaccine) and PPV (Pneumococcal Polysaccharide Vaccine) were implemented in the Netherlands for children an older adults, respectively. However, both vaccines are based on the polysaccharide of the bacteria and are therefore only capable of inducing capsule-specific antibody production. Hence, clearance of the bacteria is primarily via antibody-mediated agglutination and mucociliary clearance. Moreover, there are currently >90 different serotypes identified of the capsule. While both vaccines are highly effective, they only provide selective coverage for up to 23 serotypes. This incomplete protection facilitated gradual shifts in carriage of serotypes not included in the vaccines in all age groups, known as serotype replacement. The various shortcomings of the serotype-specific immune response revealed by the vaccines stressed the importance of protein-specific immune mechanism as another essential layer in the protection against S. pneumoniae.
The protein-based immune mechanism consist mainly of protein-specific memory B cells and antibody response, and pneumococcal-specific CD4+ T-cells. In particular pneumococcal-activated CD4+ T-cells has been shown to produce IL-17A that is essential in the recruitment of phagocytes such as neutrophils and boosting their phagocytic abilities, resulting in a more efficient clearance of S. pneumoniae via opsonophagocytosis and killing. Since pneumococcal proteins are conserved between the serotypes, protein-based immune mechanisms offer a strong universal protection in a serotype-independent manner that can be built upon throughout life. Taking into account the fluctuating susceptibility to S. pneumoniae with age, it could be hypothesized that changes has taken place in the protein-specific immune mechanisms that contributed to the susceptibility, especially in the later stages of life. Therefore, the aim of this project is to have a better understanding of the protein-based immune mechanisms, in particular CD4+ T cells, against S. pneumoniae from the perspective of natural protective acquired immunity and the alterations that take place as we age.
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