Voß, Franziska
[Verfasser:in]
;
Hammerschmidt, Sven
[Akademische:r Betreuer:in];
Westendorf, Astrid M.
[Akademische:r Betreuer:in]Universität Greifswald
Immunogenicity and protectivity of surface-localized lipoproteins of Streptococcus pneumoniae
Steptococcus pneumoniae (pneumococcus) represents a common colonizer of the human upper respiratory tract (URT). However, under certain conditions, for example following viral infections, or in indiciduals with a weakened immune system, including young children, elderly and immunocompromised persons, it can cause a wide range of life-threatening diseases, such as pneumonia, meningitis or sepsis. Based on the polysaccharide capsule that surrounds the bacterium, pneumococci are classified into so far 98 different serotypes. Prevention of S. pneumoniae infections was achieved by the development of pneumococcal polysaccharide-based (PPSV) vaccines. However, these vaccines have important limitations, including high manufacturing costs and restricted serotype coverage facilitating replacement by non-vaccine serotypes. Aiming for the development of a serotype-independent vaccine, the potential of surface-exposed and highly conserved pneumococcal lipoproteins was evaluated for being targeted as a future protein-based vaccine. Therefore, selected lipoproteins were examined i) for their surface abundance and accessibility, ii) for their presence in clinically relevant S. pneumoniae strains, and iii) for their immunogenicity. Finally, based on these initial screenings, the most promising candidates were selected to analyze their protective efficacy in a moude model of colonization. DacB and PnrA were identified as highly abundant lipoproteins on the pneumococcal surface. They showed to ...