Disentangling serotype diversity and the corresponding patterns of immunity in Streptococcus pyogenes (360G-Wellcome-218669_Z_19_Z)

Group A Streptococcus (GAS) causes a wide range of diseases, from pharyngitis and scarlet fever to potentially fatal invasive disease. GAS bacteria can be subdivided into serotypes (emm-types), grouped in emm-clusters. The existence of serotype-specific immunity following infection is established, however the extent of cross-strain protection, has not been measured. Using a combination of longitudinal cohort, surveillance and genomic data, I will use transmission-dynamic modelling and learn genomic analysis to infer the protective efficacy of naturally acquired immunity to GAS, including the extent of type-specific and heterotypic immunity. I will identify whether there is a biological basis for emm-cluster-level immunity – including whether emm-types predicted to produce immune cross-reactivity map to genetic similarity, or exhibit similarities in horizontally-acquired non-emm antigens. I will analyse the evolutionary epidemiological dynamics of GAS, to determine whether patterns of emm-type and emm-cluster prevalence over time can be explained by demographic replacement of susceptible individuals, or immune escape via pathogen evolution. The results of these analyses will allow me to inform key public health questions, including predicting the population-level impact of introducing a test-and-treat strategy for pharyngitis in UK children, and predicting the impact of polyvalent incomplete vaccines on antibiotic consumption in a US setting.