title: O-specific [corrected] polysaccharide conjugate vaccine-induced [corrected] antibodies prevent invasion of Shigella into Caco-2 cells and may be curative.
abstract: The O-specific polysaccharide (O-SP) domain of Shigella LPS is both an essential virulence factor and a protective antigen for this genus. A critical level of serum IgG anti-O-SP was shown to confer immunity to shigellosis, likely by complement-mediated bacteriolysis of the inoculum. Conjugate Shigella O-SP vaccines were shown to be safe and immunogenic in children, and, in a preliminary study, Shigella sonnei vaccine was protective in young adults. Characteristic of shigellosis is bacterial invasion of intestinal cells. Incubation of shigellae with postimmunization but not preimmunization sera of children vaccinated with S. sonnei or Shigella flexneri 2a O-SP conjugate vaccines inhibited in a type-specific and dose-dependent manner in vitro invasion of intestinal epithelial cells (Caco-2) and the infection-associated increases in IL-1beta and IL-8 mRNA and extracellular cytokine levels. Pretreatment of these sera or of Caco-2 cells with O-SP abrogated these effects also in a type-specific and dose-dependent manner. Confocal microscopy demonstrated antibody-specific inhibition of bacterial adhesion to HeLa cells. These protective effects were duplicated by IgG purified from these sera. These results suggest a dual role for IgG anti-O-SP. In addition to lysis of the inoculum in immune individuals, the newly synthesized IgG anti-O-SP in patients may terminate an established infection by inhibiting shigellae released from epithelial cells from invading new ones. A critical level of IgG anti-O-SP could, therefore, have a protective as well as a curative role in shigellosis.
authors.affiliation: Department of Gastroenterology, Edmond and Lily Safra Children's Hospital, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel. ychowers@post.tau.ac.il
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Chowers
authors.forename: Joachim
authors.initials: J
authors.lastname: Kirschner
authors.forename: Nathan
authors.initials: N
authors.lastname: Keller
authors.forename: Iris
authors.initials: I
authors.lastname: Barshack
authors.forename: Simon
authors.initials: S
authors.lastname: Bar-Meir
authors.forename: Shai
authors.initials: S
authors.lastname: Ashkenazi
authors.forename: Rachel
authors.initials: R
authors.lastname: Schneerson
authors.forename: John
authors.initials: J
authors.lastname: Robbins
authors.forename: Justen H
authors.initials: JH
authors.lastname: Passwell
mesh_terms: D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D000918:Antibody Specificity; D002648:Child; D016207:Cytokines / Q000096:biosynthesis; D004405:Dysentery, Bacillary / Q000517:prevention & control / Q000628:therapy*; D006367:HeLa Cells; D006801:Humans; D007074:Immunoglobulin G; D007413:Intestinal Mucosa / Q000382:microbiology / Q000473:pathology; D019081:O Antigens / Q000627:therapeutic use*; D012760:Shigella / Q000472:pathogenicity*; D022281:Shigella Vaccines / Q000627:therapeutic use*; D016896:Treatment Outcome; D018074:Vaccines, Conjugate / Q000627:therapeutic use; D037521:Virulence Factors
chemical_list: D000907:Antibodies, Bacterial; D016207:Cytokines; D007074:Immunoglobulin G; D019081:O Antigens; D022281:Shigella Vaccines; D018074:Vaccines, Conjugate; D037521:Virulence Factors