title: Protection of mice against Shiga toxin 2 (Stx2)-associated damage by maternal immunization with a Brucella lumazine synthase-Stx2 B subunit chimera.
abstract: Hemolytic-uremic syndrome (HUS) is defined as the triad of anemia, thrombocytopenia, and acute kidney injury. Enterohemorrhagic Shiga toxin (Stx)-producing Escherichia coli (EHEC), which causes a prodromal hemorrhagic enteritis, remains the most common etiology of the typical or epidemic form of HUS. Because no licensed vaccine or effective therapy is presently available for human use, we recently developed a novel immunogen based on the B subunit of Shiga toxin 2 (Stx2B) and the enzyme lumazine synthase from Brucella spp. (BLS) (BLS-Stx2B). The aim of this study was to analyze maternal immunization with BLS-Stx2B as a possible approach for transferring anti-Stx2 protection to the offspring. BALB/c female mice were immunized with BLS-Stx2B before mating. Both dams and pups presented comparable titers of anti-Stx2B antibodies in sera and fecal extracts. Moreover, pups were totally protected against a lethal dose of systemic Stx2 injection up to 2 to 3 months postpartum. In addition, pups were resistant to an oral challenge with an Stx2-producing EHEC strain at weaning and did not develop any symptomatology associated with Stx2 toxicity. Fostering experiments demonstrated that anti-Stx2B neutralizing IgG antibodies were transmitted through breast-feeding. Pups that survived the EHEC infection due to maternally transferred immunity prolonged an active and specific immune response that protected them against a subsequent challenge with intravenous Stx2. Our study shows that maternal immunization with BLS-Stx2B was very effective at promoting the transfer of specific antibodies, and suggests that preexposure of adult females to this immunogen could protect their offspring during the early phase of life.
authors.affiliation: Laboratorio de Patogénesis e Inmunología de Procesos Infecciosos, Instituto de Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas-Academia Nacional de Medicina, Buenos Aires, Argentina.
authors.forename: María Pilar
authors.initials: MP
authors.lastname: Mejias
authors.forename: Gabriel
authors.initials: G
authors.lastname: Cabrera
authors.forename: Romina Jimena
authors.initials: RJ
authors.lastname: Fernández-Brando
authors.forename: Ariela
authors.initials: A
authors.lastname: Baschkier
authors.forename: Giselle
authors.initials: G
authors.lastname: Ghersi
authors.forename: Maria Jimena
authors.initials: MJ
authors.lastname: Abrey-Recalde
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Miliwebsky
authors.forename: Roberto
authors.initials: R
authors.lastname: Meiss
authors.forename: Fernando
authors.initials: F
authors.lastname: Goldbaum
authors.forename: Vanesa
authors.initials: V
authors.lastname: Zylberman
authors.forename: Marta
authors.initials: M
authors.lastname: Rivas
authors.forename: Marina Sandra
authors.initials: MS
authors.lastname: Palermo
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis; D002002:Brucella / Q000276:immunology; D004195:Disease Models, Animal; D054324:Enterohemorrhagic Escherichia coli; D004927:Escherichia coli Infections / Q000276:immunology*; D005260:Female; D006463:Hemolytic-Uremic Syndrome / Q000382:microbiology / Q000517:prevention & control*; D007112:Immunity, Maternally-Acquired / Q000276:immunology*; D007114:Immunization / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D009097:Multienzyme Complexes / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology; D022641:Shiga Toxin 2 / Q000276:immunology*; D022281:Shigella Vaccines / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D009097:Multienzyme Complexes; D011993:Recombinant Fusion Proteins; D022641:Shiga Toxin 2; D022281:Shigella Vaccines; C450841:shiga toxin 2 B subunit; C044822:6,7-dimethyl-8-ribityllumazine synthase