TY  - JOUR
PY  - 2006//
TI  - A pilot clinical trial of a recombinant ricin vaccine in normal humans
JO  - Proceedings of the National Academy of Sciences of the United States of America
A1  - Vitetta, Ellen S.
A1  - Smallshaw, Joan E.
A1  - Coleman, Elaine
A1  - Jafri, Hasan
A1  - Foster, Callie
A1  - Munford, Robert
A1  - Schindler, John
SP  - 2268
EP  - 2273
VL  - 103
IS  - 7
N2  - Ricin, a highly potent toxin produced by castor beans, is classified by the Centers for Disease Control and Prevention as a level B biothreat because it is easily produced, readily available, and highly stable. There have been >750 cases of documented ricin intoxication in humans. There is no approved vaccine for ricin. Ricin contains a lectin-binding B chain and a ribotoxic A chain (RTA). In addition to its ribotoxic site, we have identified a separate site on RTA that is responsible for inducing vascular leak syndrome (VLS) in humans. We have generated a recombinant RTA with two amino acid substitutions that disrupt its ribotoxic site (Y80A) and its VLS-inducing site (V76M). This mutant recombinant RTA (named RiVax) was expressed and produced in Escherichia coli and purified. When RiVax was injected i.m. into mice it protected them against a ricin challenge of 10 LD50s. Preclinical studies in both mice and rabbits demonstrated that RiVax was safe. Based on these results, we have now conducted a pilot clinical trial in humans under an investigational new drug application submitted to the Food and Drug Administration. In this study, three groups of five normal volunteers were injected three times at monthly intervals with 10, 33, or 100 mug of RiVax. The vaccine was safe and elicited ricin-neutralizing Abs in one of five individuals in the low-dose group, four of five in the intermediate-dose group, and five of five in the high-dose group. These results justify further development of the vaccine.<p /> <p>Language: en</p>
LA  - en
SN  - 0027-8424
UR  - http://dx.doi.org/10.1073/pnas.0510893103
ID  - ref1
ER  -