Protection of mice against Stx2-associated damage by maternal immunization with BLS-Stx2B chimera

MEJIAS MP; CABRERA GABRIEL; FERNÁNDEZ BRANDO ROMINA J; BASCHKIER, A; GHERSI, GISELLE; ABREY-RECALDE MARIA JIMENA; MILIWEBSKY, E; MEISS R; GOLDBAUM, FERNANDO; ZYLBERMAN, VANESA; RIVAS M; PALERMO, MARINA S

INFECTION AND IMMUNITY

AMER SOC MICROBIOLOGY

Lugar: Washington; Año: 2014 vol. 82 p. 1491 - 1499

0019-9567

Hemolytic uremic syndrome (HUS) is defined as the triad of anemia, thrombocytopenia, and acute kidney injury. Enterohemorrhagic Shiga toxin (Stx)-producing Escherichia coli (EHEC) that cause a prodromal hemorrhagic enteritis remain 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 their 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 2-3 months postpartum. In addition, pups were resistant to an oral challenge with a 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 pre-exposure of adult females to this immunogen could protect their offspring during the early phase of life.