A flexible agent-based modelling framework of multi-serotype pneumococcal carriage to evaluate vaccine strategies in large populations

Streptococcus pneumoniae is a multi-serotype pathogen causing a substantial global burden of pneumonia and invasive bacterial disease. Pneumococcal conjugate vaccines have been implemented worldwide, protecting against colonisation and disease from selected high-burden serotypes, but in many settings short-term effectiveness has been eroded by serotype replacement. Vaccines with broader serotype coverage have been developed, at the cost of immunogenicity against single serotypes. To determine the longer-term impact of these new formulations, we propose a novel modelling framework that evaluates the relationship between serotype-specific vaccine immunogenicity and effectiveness, comprising immunity, carriage and clinical models. Dynamics of individual serotypes are modelled over time, advancing existing modelling paradigms that group all serotypes according to vaccine type. This framework is sufficiently flexible to consider diverse populations, emerging vaccine formulations and implementation strategies. A retrospective analysis of sequential introduction of 7- and 13-valent pneumococcal conjugate vaccines in Australia demonstrates the flexibility of the model.