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

Abstract

dIn developing countries, Shigella is 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 multiple Shigella serotypes and species. Among these, one antigen induced cross-protection against experimental shigellosis, and we have named it pan-Shigella surface 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 against Shigella flexneri serotypes 2a, 5a, and 6, Shigella boydii, Shigella sonnei, and Shigella dysenteriae serotype 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 conserved Shigella protein antigens but not to PSSP-1. We suggest that PSSP-1 is a promising antigen for a broadly protective vaccine against Shigella.

Circulating Gut-Homing (α 4 β 7 + ) Plasmablast Responses against Shigella Surface Protein Antigens among Hospitalized Patients with Diarrhea

“…This study also demonstrated that naturally induced ASC responses to PSSP1, an antigen recently identified as cross-protec- tive in animal studies (35), were rather infrequent and generally much weaker than the corresponding ASC responses to IpaD (and, for that matter, IpaC). This observation may indicate that such mucosal antibody responses may not develop to a level conducive to immune protection or may wane too rapidly after Shigella infection to support protection against subsequent reinfection by Shigella bacteria of the same or different species and serotypes.…”

“…Recent preclinical studies showed that IpaD and PSSP1 antigens can induce cross-protection against experimental shigellosis caused by several species and serotypes (35,43). We thus compared gut-homing ASC responses to IpaD20/IpaD120 and PSSP1 among shigellosis patients.…”

“…Furthermore, Ipas have been shown to be protective in animal studies (32)(33)(34). More recently, a novel and potentially cross-protective protein antigen, termed pan-Shigella surface protein 1 (PSSP1), has been identified on the C terminus of Shigella outer membrane protease IcsP and is conserved among all Shigella species and serotypes (35). Another, albeit less conserved, epitope called PSSP2 has also been identified as part of SigA, an autotransporter-like protease (36).…”

Cross-Protective Shigella Whole-Cell Vaccine With a Truncated O-Polysaccharide Chain

“…Evidence for masking of Shigella surface proteins is provided by our studies of pan Shigella surface protein-1 (PSSP-1) the C-terminal half-polypeptide of IcsP (Fukuda et al, 1995 ) that is conserved across Shigella species (Kim et al, 2015 ). We found that PSSP-1-specific antibodies did not bind IcsP on Shigella cells, which was consistent with another report that LPS Oag of gram-negative bacteria masks other surface antigens, such as IcsP ( S. flexneri ), by preventing antibody access (van der Ley et al, 1986 ; Tran et al, 2013 ).…”

Natural avirulentShigella boydiistrain in the Brazilian Amazon lacks major virulence genes and present Type II, Type III and Type VI Secretion Systems

“…Still, IFNγ is known to be involved in protection against Shigella infections and response to subunit polypeptide vaccines (48). Surprisingly, S. boydii str.…”