The infectious disease, diphtheria, is cause by toxigenic strains of Corynebacterium diphtheriae. The introduction of mass vaccination worldwide has led to a global decrease in incidents of diphtheria, however, there has been a significant rise in reported cases globally in recent years. The diphtheria toxoid vaccine, made from inactivated toxin, induces antibody production for neutralising the toxin. However, it is not effective against non-toxigenic strains that are causing severe invasive infections and may have limited efficacy against emerging toxin variants with structural modifications of the toxin which may escape the vaccine. Furthermore, multidrug resistance among these strains is limiting the treatment options, highlighting a need for a new vaccine that is effective against all C. diphtheriae strains. We have identified three highly conserved proteins within this species using reverse vaccinology and computational approaches that would be highly suitable vaccine candidates (unpublished data). We have cloned these proteins in Escherichia coli vector, overexpressed and purified them for immunogenic characterisation against sera samples from immunised volunteers. We are also using microarray-hybridisation based approaches and ELISpot assays to map B-cell and T-cell response against these proteins. Initial results show that these proteins contain highly immunogenic peptides that may be suitable for developing a more effective vaccine against all C. diphtheriae strains.