Figure 3

Population structure and vaccination. Conceptual representation of phylogenetic relationships between serotypes and Sequence Clusters (SC), where the former are defined by variation at the cps locus (arbitrarily designated X, W, Y, Z, M, and L, respectively coloured purple, yellow, green, orange, cyan and pink) and the latter are linked to variation in the groESL operon (arbitrarily designated A and B and respectively coloured red and blue). Circles symbolize genotypes, with size relative to their prevalence at the population level. Inner genome arcs represent epistatic links: those with the groESL operon extend across the genome, while links with the cps locus are more local. Within our framework and according to observed patterns⁸, serotypes will be dominantly associated with an SC. Current vaccine strategies (white inner area) that target a selection of capsular serotypes can lead to the expansion of non-vaccine serotypes (VISR^{73, 74}), potentially within the same sequence cluster (VIMS¹⁷). Vaccine strategies based on groESL variants (grey area) would target entire lineages instead, including all uncommon serotypes within and thereby preventing their expansion.