Insights into the Differential Cytotoxicity of Abrin and Design of a Vaccine Candidate against the Toxin

Abstract

Ribosome inactivating proteins (RIPs) from plants, fungi or bacteria are extremely lethal due to their N-glycosidase activity on eukaryotic ribosomal RNA. As the name indicates, these toxins inactivate ribosomes; thereby inhibit protein synthesis leading to cell death. The plant toxin, abrin, a type-II RIP, is extremely lethal, the human fatal dose being ~1 μg/kg body weight. On one hand, the high toxic property of abrin has been employed in generating immunotoxins, for cell-targeted killing, while on the other; abrin has been classified as an agent for bioterrorism by the Centre for Disease Control and Prevention, U.S.A., because of ease or purification, its stability thereafter and, toxicity at very low concentrations. Apart from inhibition of protein synthesis abrin also induces programmed cell death. The present study focuses on gaining insights into the mechanisms by which abrin induces apoptosis. The study also aims to develop a vaccine candidate against abrin toxicity. In conclusion, we have developed a chimeric Abrus protein based on the neutralizing epitopes for mAbs D6F10 and A7C4, the only neutralizing antibodies against abrin reported till now. The present data shows that the chimera has good immunogenicity and immunoreactivity. We observed that the chimera induced neutralizing antibodies that could neutralize even as high as 45-50 X LD50 doses of abrin and also protected 100 percent mice from abrin-induced death. Taken altogether, the chimera can serve as a promising vaccine against the deadly toxin, abrin