PLGA-based nanovaccine delivering chimeric IpaD-StxB protein induces robust immune response against Shigella infection.

Abstract

BACKGROUND AND AIM: Shigellosis is a major cause of morbidity and mortality worldwide, especially among children under five in low- and middle-income countries. Despite its public health burden, there is no licensed vaccine. Recombinant and nanoparticle-based vaccine approaches offer promising alternatives to conventional methods. This study aimed to develop a chimeric nanovaccine based on the fusion of Shigella flexneri IpaD and StxB, encapsulated in PLGA nanoparticles, and to evaluate its immunogenic potential in a murine model. METHODS: The recombinant IpaD-StxB (IdSb) protein was expressed in E. coli, purified under denaturing conditions, and encapsulated into PLGA nanoparticles using a double emulsion solvent evaporation technique. Particle size, morphology, encapsulation efficiency, and in vitro release were characterized. BALB/c mice were immunized with either Nano-IdSb or free IdSb, and serum IgG levels were assessed via ELISA to evaluate the humoral immune response. RESULTS: The 24 kDa recombinant IdSb protein was successfully expressed in a prokaryotic system, yielding 10 mg/mL. PLGA nanoparticles encapsulating IdSb had an average diameter of 166 nm, high encapsulation efficiency (97%), and a loading capacity of 3.5%. They enabled sustained protein release over 40 days. Mice immunized with Nano-IdSb exhibited significantly stronger IgG responses than those receiving the free protein, indicating enhanced immunogenicity and antigen stability. CONCLUSION: PLGA-encapsulated IdSb nanovaccine elicited a robust humoral immune response and demonstrated favorable physicochemical properties, supporting its potential as a cost-effective and broadly protective vaccine candidate against Shigella spp.