Intradermal delivery of Shigella IpaB and IpaD type III secretion proteins: kinetics of cell recruitment and antigen uptake, mucosal and systemic immunity, and protection across serotypes.

Broadly protective Shigella vaccine based on type III secretion apparatus proteins.

Shigella spp. are food- and waterborne pathogens that cause severe diarrheal and dysenteric disease associated with high morbidity and mortality. Individuals most often affected are children under 5 years of age in the developing world. The existence of multiple Shigella serotypes and the heterogenic distribution of pathogenic strains, as well as emerging antibiotic resistance, require the deve...

Mucosal and Systemic Immunity, and Cell Recruitment and Antigen Uptake, IpaD Type III Secretion Proteins: Kinetics

Bile salts stimulate recruitment of IpaB to the Shigella flexneri surface, where it colocalizes with IpaD at the tip of the type III secretion needle.

Shigella flexneri uses its type III secretion apparatus (TTSA) to deliver invasins into human cells. This TTSA possesses an external needle with IpaD at its tip. We now show that deoxycholate promotes the stable recruitment of IpaB to the needle tip without inducing a rapid burst of type III secretion. The maintenance of IpaB at the needle tip requires a stable association of IpaD with the Shig...

Liposomes recruit IpaC to the Shigella flexneri type III secretion apparatus needle as a final step in secretion induction.

Shigella flexneri contact with enterocytes induces a burst of protein secretion via its type III secretion apparatus (TTSA) as an initial step in cellular invasion. We have previously reported that IpaD is positioned at the TTSA needle tip (M. Espina et al., Infect. Immuno. 74:4391-4400, 2006). From this position, IpaD senses small molecules in the environment to control the presentation of Ipa...

Shigella IpaB and IpaD displayed on L. lactis bacterium-like particles induce protective immunity in adult and infant mice

Shigella spp. are among the enteric pathogens with the highest attributable incidence of moderate-to-severe diarrhea in children under 5 years of age living in endemic areas. There are no vaccines available to prevent this disease. In this work, we investigated a new Shigella vaccine concept consisting of nonliving, self-adjuvanted, Lactococcus lactis bacterium-like particles (BLP) displaying S...