A novel recombinant vaccine which protects mice against ricin intoxication

Joan E. Smallshaw; Ana Firan; John R. Fulmer; Stephen L. Ruback; Victor Ghetie; Ellen S. Vitetta

doi:10.1016/S0264-410X(02)00312-2

A novel recombinant vaccine which protects mice against ricin intoxication

Joan E. Smallshaw, Ana Firan, John R. Fulmer, Stephen L. Ruback, Victor Ghetie, Ellen S. Vitetta

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

93 Scopus citations

Abstract

Ricin toxin (RT) is a plant-derived toxin of extraordinary toxicity; a single molecule successfully internalized into the cytoplasm of a cell is lethal for that cell. An estimated dose of 1-10μg/kg is lethal to humans, making aerosolized ricin a potential agent for bioterrorism. Vaccination against ricin using either denatured toxin or its modified A chain subunit (RTA) has been successful in experimental animals but both vaccines have potential toxicities. Recombinant (r) RTA has not been evaluated as a vaccine. However, the advantage of such a vaccine is that these potential toxicities can be deleted by appropriate mutations. In this study we have generated three mutants and shown that two lack toxicity as compared to the wild type rRTA. These mutants induce protective humoral immune responses in mice. One or both should be considered for use in humans.

Original language	English (US)
Pages (from-to)	3422-3427
Number of pages	6
Journal	Vaccine
Volume	20
Issue number	27-28
DOIs	https://doi.org/10.1016/S0264-410X(02)00312-2
State	Published - Sep 10 2002

Keywords

Bioterrorism
Mutation
Ricin

ASJC Scopus subject areas

Molecular Medicine
General Immunology and Microbiology
General Veterinary
Public Health, Environmental and Occupational Health
Infectious Diseases

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10.1016/S0264-410X(02)00312-2

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title = "A novel recombinant vaccine which protects mice against ricin intoxication",

abstract = "Ricin toxin (RT) is a plant-derived toxin of extraordinary toxicity; a single molecule successfully internalized into the cytoplasm of a cell is lethal for that cell. An estimated dose of 1-10μg/kg is lethal to humans, making aerosolized ricin a potential agent for bioterrorism. Vaccination against ricin using either denatured toxin or its modified A chain subunit (RTA) has been successful in experimental animals but both vaccines have potential toxicities. Recombinant (r) RTA has not been evaluated as a vaccine. However, the advantage of such a vaccine is that these potential toxicities can be deleted by appropriate mutations. In this study we have generated three mutants and shown that two lack toxicity as compared to the wild type rRTA. These mutants induce protective humoral immune responses in mice. One or both should be considered for use in humans.",

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AU - Smallshaw, Joan E.

AU - Firan, Ana

AU - Fulmer, John R.

AU - Ruback, Stephen L.

AU - Ghetie, Victor

AU - Vitetta, Ellen S.

PY - 2002/9/10

Y1 - 2002/9/10

N2 - Ricin toxin (RT) is a plant-derived toxin of extraordinary toxicity; a single molecule successfully internalized into the cytoplasm of a cell is lethal for that cell. An estimated dose of 1-10μg/kg is lethal to humans, making aerosolized ricin a potential agent for bioterrorism. Vaccination against ricin using either denatured toxin or its modified A chain subunit (RTA) has been successful in experimental animals but both vaccines have potential toxicities. Recombinant (r) RTA has not been evaluated as a vaccine. However, the advantage of such a vaccine is that these potential toxicities can be deleted by appropriate mutations. In this study we have generated three mutants and shown that two lack toxicity as compared to the wild type rRTA. These mutants induce protective humoral immune responses in mice. One or both should be considered for use in humans.

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A novel recombinant vaccine which protects mice against ricin intoxication

Abstract

Keywords

ASJC Scopus subject areas

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