The role of pneumococcal protein antigens in immune cell stimulation and novel vaccine delivery methods for immunisation

Abstract

Streptococcus pneumoniae remains one of the most deadly pathogens worldwide, causing pneumonia, sepsis and meningitis, as well as significant morbidity and mortality. This study examines the virulence and host immune cell responses to three pneumococcal strains: serotype two (D39) and its pneumolysin-negative isogenic mutant (D39Ply-/-), and highly invasive serotype one strain (ST217). Immune responses were examined in vitro against these three strains using THP1-derived macrophage and dendritic cells at diVerent time points. Notably, significant variations were observed in growth patterns, hemolytic activity, and capsule thickness among these diVerent pneumococcal strains. Importantly, the toxin pneumolysin and capsule thickness were key factors influencing the pathogenicity and virulence of ST217. Another major aspect of my work was the identification of potential vaccine candidates. To achieve this, I examined the immunogenic components of pneumococcal cell culture supernatant (CCS) from D39, D39Ply-/-, and ST217 by incubating the CCS with antigen-presenting cells such as macrophages and dendritic cells in-vitro and identifying the proteins using a mass-spectrometry approach.