Development of a hybrid Shiga holotoxoid vaccine to elicit heterologous protection against Shiga toxins types 1 and 2.
The hemolytic uremic syndrome is a life-threatening sequela that occurs after infection with Shiga toxin (Stx)-producing Escherichia coli (STEC) or Shigella dysenteriae type 1, and Stx is responsible for initiating this syndrome. An STEC isolate can express Stx1, Stx2, or both, but antisera to Stx1 and Stx2 are not cross-neutralizing. To produce a single vaccine candidate against both toxins, we created a genetic toxoid that contained the enzymatically-inactivated StxA2 subunit and the native StxB1 subunit. We found that mice immunized with this hybrid holotoxoid, developed neutralizing anti-Stx1 and anti-Stx2 antibodies and survived challenge with 10 lethal doses of either or both toxins.
Smith
Michael J
MJ
Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Room B4052, 4301 Jones Bridge Road, Bethesda, MD 20814-4799, USA.
Teel
Louise D
LD
Carvalho
Humberto M
HM
Melton-Celsa
Angela R
AR
O'Brien
Alison D
AD
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001483:Base Sequence; D002522:Chlorocebus aethiops; D017931:DNA Primers / Q000235:genetics; D004269:DNA, Bacterial / Q000235:genetics; D004927:Escherichia coli Infections / Q000276:immunology / Q000517:prevention & control; D022361:Escherichia coli Vaccines / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009500:Neutralization Tests; D022622:Shiga Toxin 1 / Q000235:genetics* / Q000276:immunology* / Q000633:toxicity; D022641:Shiga Toxin 2 / Q000235:genetics* / Q000276:immunology* / Q000633:toxicity; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D014709:Vero Cells
D000907:Antibodies, Bacterial; D017931:DNA Primers; D004269:DNA, Bacterial; D022361:Escherichia coli Vaccines; D022622:Shiga Toxin 1; D022641:Shiga Toxin 2; D014614:Vaccines, Synthetic