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

Area of Science:

• Microbiology
• Vaccinology
• Infectious Diseases

Background:

• Shigellosis, caused by Shigella species, presents a significant global health challenge with high morbidity, mortality, and increasing antimicrobial resistance.
• Existing Shigella vaccine candidates often exhibit limited immunogenicity, reactogenicity, or cross-serotype protection due to targeting variable O-polysaccharides.

Purpose of the Study:

• To evaluate mRNA vaccine candidates targeting conserved Shigella invasion plasmid antigens (IpaB and IpaC) as a potential broad-spectrum preventive strategy.
• To assess the immunogenicity and protective efficacy of lipid nanoparticle (LNP)-encapsulated mRNA vaccines against Shigella infection.

Main Methods:

• Development of mRNA vaccine candidates encoding Shigella IpaB and IpaC antigens.
• Encapsulation of mRNA constructs into lipid nanoparticles (LNPs).
• Assessment of immune responses and protective efficacy in a mouse intraperitoneal infection model.

Main Results:

• The LNP-encapsulated mRNA vaccine induced neutralizing antibodies against Shigella.
• These antibodies demonstrated the ability to inhibit intracellular invasion by Shigella flexneri.
• The vaccine showed potential for protection against Shigella flexneri infection in a mouse model.

Conclusions:

• mRNA vaccine technology targeting conserved antigens like IpaB and IpaC offers a promising approach to overcome limitations of previous Shigella vaccines.
• The study demonstrates functional immune responses and potential protection against Shigella flexneri, supporting further research into mRNA-based Shigella vaccines.
• These findings contribute to the development of novel strategies for preventing shigellosis, a major public health concern.