Bacterial mimetic vesicles as a novel vaccine against Streptococcus pneumoniae infection

• Main Author: Zhang, Xiao Tong
• Other Authors: Czarny Bertrand Marcel Stanislas
• Format: Final Year Project
• Language: English
• Published: Nanyang Technological University 2024
• Subjects: Engineering; Medicine, Health and Life Sciences
• Online Access: https://hdl.handle.net/10356/176368
• Institution: Nanyang Technological University

Streptococcus pneumoniae (SP) is the leading cause of pneumonia, meningitis, and bacteremia acquired in the community. The 13-valent pneumococcal conjugate vaccination (PCV13) available on the market has significantly reduced the prevalence of pneumococcal illness, providing significant benefits for public health. The primary surface feature of SP is its polysaccharide capsule, which holds considerable importance in its virulence. This capsule serves as the primary focus of existing pneumococcal vaccines. However, with 100 polysaccharide serotypes currently identified, vaccine protection is specific to serotypes. These vaccinations are widely used, causing alterations in the serotype prevalence in carrier states and illness occurrences. This phenomenon is commonly referred to as "serotype replacement", identified after the launch of the 7-valent pneumococcal conjugate vaccine (PCV7) and has also been noted with other PCVs. Hence, even with the introduction of vaccinations with greater valence, serotype replacement is likely to continue. However, developing vaccinations independent of serotypes might provide a way around this problem. Bacterial extracellular vesicles (EVs) promise as vaccine candidates due to their ability to elicit immune responses, better serotype coverage, and streamlined manufacturing processes. However, isolating only natural vesicles is time-consuming and results in low yields. Therefore, this project aims to investigate the suitability of both natural and mimetic bacterial extracellular vesicles as potential vaccine candidates. In this project, we successfully isolated natural and mimetic vesicles from SP serotypes 4 and 6B. This resulted in a high protein concentration and particles for natural extracellular vesicles. However, the yield for mimetic extracellular vesicles was comparatively lower due to suboptimal growth conditions and isolation steps. Additionally, the RT-qPCR results demonstrated the potential of both natural and mimetic extracellular vesicles to induce a substantial immunogenic response in the host, thus positioning them as promising vaccine candidates.