Neutralizing antibodies induced by IpaB and IpaC mRNA vaccines inhibit Shigella flexneri invasion

Shigellosis, caused by Shigella 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 Shigella 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 Shigella invasion plasmid antigens (IpaB and IpaC), aiming to provide a preventive strategy that can address various serogroups of Shigella . 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 Shigella flexneri , confirming its potential for protection against this serotype. IMPORTANCE This study aimed to utilize mRNA vaccine technology targeting conserved antigens (IpaB and IpaC) to overcome the limitations of previous Shigella vaccines. By demonstrating functional immune responses against Shigella flexneri , our findings suggest that mRNA vaccines may serve as a preventive strategy against Shigella infection and contribute to the foundation for future research.