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Immunization with BLS-Stx2B chimera totally protects dams from early pregnancy loss induced by Shiga toxin type 2 (Stx2) and confers anti-Stx2 immunity to the offspring
Affiliation:1. Laboratorio de Fisiopatogenia, Departamento de Fisiología, Instituto de Fisiología y Biofísica Bernardo Houssay (IFIBIO Houssay-CONICET), Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina;2. Laboratorio de Patogénesis e Inmunología de Procesos Infecciosos, Instituto de Medicina Experimental, (IMEX-CONICET), Academia Nacional de Medicina, Buenos Aires, Argentina;1. Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Japan;2. Department of Orthopaedic Surgery, National Hospital Organization, Chiba Medical Center, Japan;3. Department of Bioenvironmental Medicine Graduate School of Medicine Chiba University, Japan;4. Department of Orthopaedic Surgery, Chiba Children''s Hospital, Japan;5. Dept of Orthopaedic Surgery, Sainou Hospital, Japan;1. Department of Animal Reproduction and Veterinary Radiology, School of Veterinary Medicine and Animal Science, UNESP, Distrito de Rubião Junior s/n, CEP 18618-970 Botucatu, SP, Brazil;2. Department of Veterinary Clinic, School of Veterinary Medicine and Animal Science, UNESP, Distrito de Rubião Junior s/n, CEP 18618-970 Botucatu, SP, Brazil;3. Department of Veterinary Hygiene and Public Health, School of Veterinary Medicine and Animal Science, UNESP, Distrito de Rubião Junior s/n, CEP 18618-970 Botucatu, SP, Brazil;1. Spine Surgery Group, 900, Santa Casa de Misericórdia de Santos, Brazil;2. Department of Orthopedics and Traumatology, Faculdade de Ciências Médicas, Santa Casa de Misericórdia de São Paulo, Brazil;1. Division of Pathology and Bacteriology, Fukuoka Institute of Health and Environmental Sciences, Fukuoka, Japan;2. Division of Bacteriology, Chiba Prefectural Institute of Public Health, Chiba, Japan;3. Department of Microbiology and Molecular Genetics, Graduate School of Pharmaceutical Science, Chiba University, Chiba, Japan;1. Department of Statistics, UW-Madison, 1220 Medical Sciences Center, 1300 University Avenue, Madison, WI 53706, USA;2. Department of Medical Sciences, School of Veterinary Medicine, UW-Madison, 2015 Linden Drive, Madison, WI 53706, USA;3. Department of Bacteriology, UW-Madison, 1550 Linden Drive, Madison, WI 53706, USA;4. Veterinary Integrative Biosciences, 4458 Texas A&M University, College Station, TX 77843, USA
Abstract:Shiga toxin producing Escherichia coli (STEC) are bacterial pathogens involved in food-borne diseases. Shiga toxin (Stx) is the main virulence factor of STEC and is responsible for systemic complications including Hemolytic Uremic Syndrome (HUS). It has been previously demonstrated that Shiga toxin type 2 (Stx2) induces pregnancy loss in rats in early stage of pregnancy. The main purpose of this study was to determine if an active immunization prevents Stx2 mediated pregnancy loss and confers passive protective immunity to the offspring. For that purpose Sprague Dawley female rats were immunized with the chimera based on the enzyme lumazine synthase from Brucella spp. (BLS) and the B subunit of Shiga toxin 2 (Stx2B) named BLS-Stx2B. After immunization females were mated with males. At day 8 of gestation, dams were challenged intraperitoneally with a sublethal and abortifacient dose of Stx2. The immunization induced high anti-Stx2B-specific antibody titers in sera and most important, prevented pregnancy loss. Pups born and breastfeed by immunized dams had high anti-Stx2B-specific antibody titers in sera. Cross-fostering experiments indicated that passive protective immunity against Stx2 was transmitted through lactation. These results indicate that immunization of adult female rats with BLS-Stx2B prevents Stx2-induced pregnancy loss and confers anti Stx2 protective immunity to the offspring.
Keywords:Antibodies  Vaccination  Rats  Pregnancy  Lactation
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