Preclinical toxicity and efficacy testing of RiVax, a recombinant protein vaccine against ricin.
Ricin toxin is a plant-derived ribosome inactivating protein (RIP) of extraordinary toxicity. Vaccination using ricin toxoid or its A chain (RTA) is protective in animals but both vaccines have two potential toxicities, RIP and vascular leak syndrome (VLS). Previously we described three recombinant RTA constructs from which both toxicities were eliminated by site-specific mutations. One mutant, V76M/Y80A, RiVax, has now been further characterized for immunogenicity and toxicity in animals. We have found that RiVax is safe at doses of at least 8 mg in mice, 800-fold higher than the protective dose, and induces neutralizing antibodies in both mice and rabbits.
Smallshaw
Joan E
JE
The Cancer Immunobiology Center, UT Southwestern Medical Center at Dallas, 6000 Harry Hines Blvd, NB9.210, Dallas, TX 75390-8576, USA.
Richardson
James A
JA
Pincus
Seth
S
Schindler
John
J
Vitetta
Ellen S
ES
D000818:Animals; D000906:Antibodies / Q000097:blood; D000911:Antibodies, Monoclonal / Q000276:immunology; D005260:Female; D007106:Immune Sera / Q000276:immunology; D008297:Male; D051379:Mice; D011817:Rabbits; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology / Q000633:toxicity; D012276:Ricin / Q000276:immunology*; D014612:Vaccines; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology* / Q000633:toxicity
D000906:Antibodies; D000911:Antibodies, Monoclonal; D007106:Immune Sera; D011994:Recombinant Proteins; C509236:RiVax; D014612:Vaccines; D014614:Vaccines, Synthetic; D012276:Ricin