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

SACERDOTI FLAVIA; MEJIAS MARÍA P; BRUBALLA ANDREA C; ALVAREZ ROMINA; AMARAL MARÍA MARTA; PALERMO MARINA; IBARRA CRISTINA

VACCINE

ELSEVIER SCI LTD

Lugar: Amsterdam; Año: 2016 vol. 34 p. 4732 - 4737

0264-410X

<!-- /* Font Definitions */@font-face{font-family:Arial;panose-1:2 11 6 4 2 2 2 2 2 4;mso-font-charset:0;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:3 0 0 0 1 0;}@font-face{font-family:Arial;panose-1:2 11 6 4 2 2 2 2 2 4;mso-font-charset:0;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:3 0 0 0 1 0;}@font-face{font-family:Calibri;panose-1:2 15 5 2 2 2 4 3 2 4;mso-font-charset:0;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:3 0 0 0 1 0;}@font-face{font-family:Cambria;panose-1:2 4 5 3 5 4 6 3 2 4;mso-font-charset:0;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:3 0 0 0 1 0;} /* Style Definitions */p.MsoNormal, li.MsoNormal, div.MsoNormal{mso-style-unhide:no;mso-style-qformat:yes;mso-style-parent:"";margin-top:0cm;margin-right:0cm;margin-bottom:10.0pt;margin-left:0cm;line-height:115%;mso-pagination:widow-orphan;font-size:11.0pt;font-family:Calibri;mso-fareast-font-family:Calibri;mso-bidi-font-family:"Times New Roman";mso-ansi-language:ES-AR;mso-fareast-language:EN-US;}.MsoChpDefault{mso-style-type:export-only;mso-default-props:yes;font-size:10.0pt;mso-ansi-font-size:10.0pt;mso-bidi-font-size:10.0pt;font-family:Cambria;mso-ascii-font-family:Cambria;mso-fareast-font-family:Cambria;mso-hansi-font-family:Cambria;}@page WordSection1{size:612.0pt 792.0pt;margin:70.85pt 3.0cm 70.85pt 3.0cm;mso-header-margin:36.0pt;mso-footer-margin:36.0pt;mso-paper-source:0;}div.WordSection1{page:WordSection1;}--><!-- /* Font Definitions */@font-face{font-family:Arial;panose-1:2 11 6 4 2 2 2 2 2 4;mso-font-charset:0;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:3 0 0 0 1 0;}@font-face{font-family:"Cambria Math";panose-1:2 4 5 3 5 4 6 3 2 4;mso-font-charset:0;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:3 0 0 0 1 0;}@font-face{font-family:Calibri;panose-1:2 15 5 2 2 2 4 3 2 4;mso-font-charset:0;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:3 0 0 0 1 0;}@font-face{font-family:Cambria;panose-1:2 4 5 3 5 4 6 3 2 4;mso-font-charset:0;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:3 0 0 0 1 0;} /* Style Definitions */p.MsoNormal, li.MsoNormal, div.MsoNormal{mso-style-unhide:no;mso-style-qformat:yes;mso-style-parent:"";margin-top:0cm;margin-right:0cm;margin-bottom:10.0pt;margin-left:0cm;line-height:115%;mso-pagination:widow-orphan;font-size:11.0pt;font-family:Calibri;mso-fareast-font-family:Calibri;mso-bidi-font-family:"Times New Roman";mso-ansi-language:ES-AR;mso-fareast-language:EN-US;}.MsoChpDefault{mso-style-type:export-only;mso-default-props:yes;font-size:10.0pt;mso-ansi-font-size:10.0pt;mso-bidi-font-size:10.0pt;font-family:Cambria;mso-ascii-font-family:Cambria;mso-fareast-font-family:Cambria;mso-hansi-font-family:Cambria;}@page WordSection1{size:612.0pt 792.0pt;margin:70.85pt 3.0cm 70.85pt 3.0cm;mso-header-margin:36.0pt;mso-footer-margin:36.0pt;mso-paper-source:0;}div.WordSection1{page:WordSection1;}-->Shiga toxin producing Escherichia coli (STEC) are bacterial pathogens involved infood-borne diseases. Shiga toxin (Stx) is the main virulence factor of STEC andis responsible for systemic complications including Hemolytic Uremic Syndrome(HUS). It has been previously demonstrated that Shiga toxintype 2 (Stx2) induces pregnancy loss in rats in early stage of pregnancy. Themain purpose of this study was to determine if an active immunization prevents Stx2mediated pregnancy loss and confers passive protective immunity to theoffspring. For that purpose Sprague Dawley female rats were immunized with thechimera 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 ofgestation, dams were challenged intraperitoneally with a sublethal and abortifacientdose of Stx2. The immunization induced high anti-Stx2B-specific antibody titersin sera and most important, prevented pregnancy loss. Pups born and breastfeedby immunized dams had high anti-Stx2B-specific antibody titers in sera. Cross-fosteringexperiments indicated that passive protective immunity against Stx2 wastransmitted through lactation. These results indicate that immunizationof adult female rats with BLS-Stx2B prevents Stx2-induced pregnancy loss andconfers anti Stx2 protective immunity to the offspring.