Pneumococcal colonisation models of the nasopharynx: The role of virulence factors and host immunity during colonisation

The human nasopharynx is the most important ecological niche for Streptococcus pneumoniae and the establishment of nasopharyngeal carriage is an essential pre-requisite to invasive pneumococcal disease. Virulence factors which mediate long term carriage and the immunogenicity of individual bacterial components are of interest to the development of vaccines which currently fall short of protecting against >90 known serotypes of pneumococci. This thesis contains a long term mouse model of nasopharyngeal carriage conducted in outbred mice, using both wild type and attenuated isogenic mutant pneumococcal strains. Whilst serotype-2 (D39) and serotype-3 (A66) pneumococci were carried asymptomatically in the nasopharynx for at least 21 days, mutants that lacked neuraminidases, PspA and pneumolysin were cleared from the nasopharynx 28 days to