Background:
Protein-based meningococcal vaccines such as 4CMenB target highly variable surface antigens, making prediction of vaccine coverage challenging. Current approaches, including MenDeVAR, MATS and gMATs [1-3], provide useful but limited resolution. Antigenic cartography, widely used in influenza [4], enables visualisation of antigenic relationships between strains and has potential to improve prediction of cross-reactivity in N. meningitidis.
Methods:
Antigenic cartography was adapted using sequence-based antigenic distance metrics across key vaccine antigens, including outer membrane vesicle (OMV) components (n=30). Antigenic distances were integrated with available immunological data, including IgG microarray datasets from 4CMenB-vaccinated individuals [5]. The approach was applied to a collection of N. meningitidis genomes (n=8,770), and antigenic maps were generated to identify clusters and relationships between strains. Outputs were compared with MenDeVAR predictions and mapped onto population structure using cgMLST [6].
Results:
Antigenic cartography identified distinct clustering patterns across meningococcal populations consistent with known antigenic variation, including for example fHbp. Compared to MenDeVAR, antigenic cartography provided increased resolution in distinguishing antigenic similarity between isolates. Integration with IgG data enabled identification of putative cross-reactive antigenic variants. Mapping antigenic clusters onto genomic lineages demonstrated heterogeneity in predicted vaccine coverage within and between meningococcal lineages.
Conclusions:
Antigenic cartography provides a scalable and high-resolution framework for assessing antigenic relationships and predicting vaccine coverage in N. meningitidis. This approach complements existing methods and enables lineage-level interpretation of vaccine impact. It has potential applications in monitoring emerging meningococcal lineages and evaluating the impact of vaccination strategies in at-risk populations, and can be extended to N. gonorrhoeae to investigate antigenic determinants underlying observed cross-protection from 4CMenB.