Neutralizing antibodies induced by IpaB and IpaC mRNA vaccines inhibit <i>Shigella flexneri</i> invasion

Shigellosis, caused by <i>Shigella</i> species, remains a significant global health burden due to its high morbidity and mortality, particularly in developing countries, and frequent antimicrobial resistance. Thus far, various <i>Shigella</i> vaccine candidates have been tested, but many have shown limited immunogenicity, high reactogenicity, or insufficient cross-serotype protection due to serotype-specific O-polysaccharide (OPS) targeting. In this study, we evaluated mRNA vaccine candidates targeting the highly conserved <i>Shigella</i> invasion plasmid antigens (IpaB and IpaC), aiming to provide a preventive strategy that can address various serogroups of <i>Shigella</i>. Using a mouse intraperitoneal infection model, we assessed the immune responses and protective efficacy of lipid nanoparticle (LNP)-encapsulated mRNA vaccines. The results demonstrated that the vaccine induced neutralizing antibodies capable of inhibiting intracellular invasion by <i>Shigella flexneri</i>, confirming its potential for protection against this serotype.IMPORTANCEThis study aimed to utilize mRNA vaccine technology targeting conserved antigens (IpaB and IpaC) to overcome the limitations of previous <i>Shigella</i> vaccines. By demonstrating functional immune responses against <i>Shigella flexneri</i>, our findings suggest that mRNA vaccines may serve as a preventive strategy against <i>Shigella</i> infection and contribute to the foundation for future research.