Development of a hybrid Shiga holotoxoid vaccine to elicit heterologous protection against Shiga toxins types 1 and 2

Michael J. Smith; Louise D. Teel; Humberto M. Carvalho; Angela R. Melton-Celsa; Alison D. O'Brien

doi:10.1016/j.vaccine.2006.02.035

Development of a hybrid Shiga holotoxoid vaccine to elicit heterologous protection against Shiga toxins types 1 and 2

Michael J. Smith, Louise D. Teel, Humberto M. Carvalho, Angela R. Melton-Celsa, Alison D. O'Brien^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

59 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	4122-4129
Number of pages	8
Journal	Vaccine
Volume	24
Issue number	19
DOIs	https://doi.org/10.1016/j.vaccine.2006.02.035
State	Published - 8 May 2006
Externally published	Yes

Keywords

Shiga toxin
Toxoids

Access to Document

10.1016/j.vaccine.2006.02.035

Cite this

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title = "Development of a hybrid Shiga holotoxoid vaccine to elicit heterologous protection against Shiga toxins types 1 and 2",

abstract = "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.",

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AU - Smith, Michael J.

AU - Teel, Louise D.

AU - Carvalho, Humberto M.

AU - Melton-Celsa, Angela R.

AU - O'Brien, Alison D.

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AB - 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.

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