Shigella Outer Membrane Protein PSSP-1 Is Broadly Protective against Shigella Infection

Abstract

ABSTRACTIn developing countries,Shigellais a primary cause of diarrhea in infants and young children. Although antibiotic therapy is an effective treatment for shigellosis, therapeutic options are narrowing due to the emergence of antibiotic resistance. Thus, preventive vaccination could become the most efficacious approach for controlling shigellosis. We have identified several conserved protein antigens that are shared by multipleShigellaserotypes and species. Among these, one antigen induced cross-protection against experimental shigellosis, and we have named it pan-Shigellasurface protein 1 (PSSP-1). PSSP-1-induced protection requires a mucosal administration route and coadministration of an adjuvant. When PSSP-1 was administered intranasally, it induced cross-protection againstShigella flexneriserotypes 2a, 5a, and 6,Shigella boydii,Shigella sonnei, andShigella dysenteriaeserotype 1. Intradermally administered PSSP-1 induced strong serum antibody responses but failed to induce protection in the mouse lung pneumonia model. In contrast, intranasal administration elicited efficient local and systemic antibody responses and production of interleukin 17A and gamma interferon. Interestingly, blood samples from patients with recent-onset shigellosis showed variable but significant mucosal antibody responses to other conservedShigellaprotein antigens but not to PSSP-1. We suggest that PSSP-1 is a promising antigen for a broadly protective vaccine againstShigella.