A novel recombinant vaccine which protects mice against ricin intoxication.
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 1-10 microg/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.
Smallshaw
Joan E
JE
The Cancer Immunobiology Center, University of Texas Southwestern Medical Center, Dallas, 6000 Harry Hines Blvd., 75390-8576, USA.
Firan
Ana
A
Fulmer
John R
JR
Ruback
Stephen L
SL
Ghetie
Victor
V
Vitetta
Ellen S
ES
D000818:Animals; D001483:Base Sequence; D023482:Bioterrorism; D018744:DNA, Plant / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D016297:Mutagenesis, Site-Directed; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D012276:Ricin / Q000235:genetics / Q000276:immunology / Q000633:toxicity*; D012278:Ricinus / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000235:genetics / Q000494:pharmacology*
D018744:DNA, Plant; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; D012276:Ricin