Shigella sonnei and Shigella flexneri: Epidemiology supporting development of cross-protective vaccines.

Shigellosis represents a major global health challenge, significantly contributing to mortality among children under five, particularly in sub-Saharan Africa and South Asia. Advances in molecular techniques have underscored the extensive global impact of Shigella, and the spread of multi- and extensively drug-resistant strains has sharply escalated the threat, emphasizing the urgent need for innovative interventions. Developing a broadly protective vaccine with a positive benefit-risk profile remains a critical and challenging objective due to the diversity of Shigella serotypes mediated by the immune dominance of the O-antigen. This review analyzes the distribution of Shigella serotypes in both endemic and non-endemic regions and examines the impact of O-antigen diversity on cross-reactivity. Various vaccine strategies, with a particular focus on the O-antigen as a key antigenic target, will be presented, highlighting the need for an effective vaccine especially due to the increased antimicrobial resistance associated to this pathogen. Overall, this review aims to provide a thorough understanding of different aspects of Shigella epidemiology with the aim to support development of effective control strategies against Shigella thus contributing to efforts against the escalating antimicrobial resistance crisis.