Colonisation of human nasopharynx with pneumococcus is frequent and the main reservoir of transmission and disease. We have developed safe and reproducible Human Infection Challenge Models, in which ~50% of inoculated participants develop nasopharyngeal pneumococcal colonisation at a density similar to natural carriage. One of the unique advantages of the human challenge model is the known timing of exposure and onset of infection episode. This has allowed us to investigate the kinetics of pneumococcal density, mucosal immune responses, and nasal shedding. More recently our model was expanded to include older adults and groups at higher risk of pneumonia. Of importance, we have identified differential host responses to pneumococcal colonisation in older adults and asthmatics which might be associated with their vulnerability to pneumococcal infection. In contrast to what we observed in young healthy adults, previous colonisation episode did not lead to protection against reacquisition of the bacteria following re-challenge. We have also co-infected participants with live attenuated influenza virus and defined key immune mechanisms at the nasal and lung mucosa by which influenza predisposes individuals to pneumococcus and by which pneumococcus alters responses to the virus. We recently established a new pneumococcal challenge model for serotype 3 (Spn3), aiming to study why Spn3 remains a leading cause of pneumococcal disease globally despite its inclusion in PCV13 and PPV23 vaccines and to identify immunological parameters that potentially correlate with protection against pneumococcal colonisation.
Our overall work has several implications for vaccine development and vaccination policy as it highlights the importance of control of colonisation density to maximise vaccination efficacy and herd immunity in vaccinated populations.