Contributions of capsule, lipoproteins and duration of colonisation towards the protective immunity of prior Streptococcus pneumoniae nasopharyngeal colonisation

Live attenuated vaccines have been proposed as a strategy to induce protective immunity against infectious diseases. Recent data have demonstrated that nasopharyngeal colonisation with Streptococcus pneumoniae induces protective immunity against subsequent invasive infection, suggesting nasal vaccination with live attenuated bacteria could be a preventative strategy. However the bacterial factors affecting the strength of this adaptive immune response remain unclear. In a direct comparison with the parent wild-type strain, we found that colonisation with bacteria lacking either capsule or surface lipoproteins led to significantly diminished protection. Immunity after colonisation was not dependent on serum IgG to capsular antigens. Colonisation density and duration was reduced for all the non-protective strains, suggesting that protective immunity maybe related to the extent of nasopharyngeal bacterial exposure. To investigate this hypothesis, we utilised an auxotrophic bacterial Δpab strain where duration of colonisation could be controlled by supply and removal of para-amino-benzoic acid (PABA) to mouse drinking water. Supporting colonisation with the Δpab strain for 5 days with PABA led to a faster serum antibody response compared to colonisation for less than 48 h. This enhanced immunogenicity was associated with a trend towards protection. The data presented here aid our understanding of why only certain live attenuated strains are able to function as effective vaccines, and may be valuable in informing the constituents of future live attenuated vaccines.