title: Shigella outer membrane protein PSSP-1 is broadly protective against Shigella infection.
abstract: In 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.
authors: Laboratory Science Division, International Vaccine Institute, Seoul, South Korea jokim@ivi.int dongwook@hanyang.ac.kr.
authors: Jae-Ouk
authors: JO
authors: Kim
authors: Laboratory Science Division, International Vaccine Institute, Seoul, South Korea.
authors: Semi
authors: S
authors: Rho
authors: Laboratory Science Division, International Vaccine Institute, Seoul, South Korea.
authors: Su Hee
authors: SH
authors: Kim
authors: Laboratory Science Division, International Vaccine Institute, Seoul, South Korea.
authors: Heejoo
authors: H
authors: Kim
authors: Laboratory Science Division, International Vaccine Institute, Seoul, South Korea.
authors: Hyo Jin
authors: HJ
authors: Song
authors: Laboratory Science Division, International Vaccine Institute, Seoul, South Korea.
authors: Eun Jin
authors: EJ
authors: Kim
authors: Laboratory Science Division, International Vaccine Institute, Seoul, South Korea.
authors: Ryang Yeo
authors: RY
authors: Kim
authors: Laboratory Science Division, International Vaccine Institute, Seoul, South Korea.
authors: Eun Hye
authors: EH
authors: Kim
authors: National Institute of Cholera and Enteric Diseases, Kolkata, India.
authors: Anuradha
authors: A
authors: Sinha
authors: Laboratory Science Division, International Vaccine Institute, Seoul, South Korea.
authors: Ayan
authors: A
authors: Dey
authors: Laboratory Science Division, International Vaccine Institute, Seoul, South Korea.
authors: Jae Seung
authors: JS
authors: Yang
authors: Laboratory Science Division, International Vaccine Institute, Seoul, South Korea.
authors: Man Ki
authors: MK
authors: Song
authors: National Institute of Cholera and Enteric Diseases, Kolkata, India.
authors: Ranjan Kumar
authors: RK
authors: Nandy
authors: Laboratory Science Division, International Vaccine Institute, Seoul, South Korea Institut de Pharmacologie Moléculaire et Cellulaire, CNRS, INSERM, Université de Nice-Sophia Antipolis, UMR 7275, Valbonne, France.
authors: Cecil
authors: C
authors: Czerkinsky
authors: Laboratory Science Division, International Vaccine Institute, Seoul, South Korea College of Pharmacy, Hanyang University, Ansan, South Korea jokim@ivi.int dongwook@hanyang.ac.kr.
authors: Dong Wook
authors: DW
authors: Kim
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D002675:Child, Preschool; D056738:Cross Protection; D004405:Dysentery, Bacillary / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D006801:Humans; D064789:Immunity, Heterologous; D007223:Infant; D007271:Injections, Intradermal; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018410:Pneumonia, Bacterial / Q000276:immunology / Q000517:prevention & control; D012760:Shigella / Q000276:immunology*; D022281:Shigella Vaccines / Q000008:administration & dosage* / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D020381:Interleukin-17; D022281:Shigella Vaccines; D007371:Interferon-gamma
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