title: A chimeric protein of abrin and Abrus precatorius agglutinin that neutralizes abrin mediated lethality in mice.
abstract: Abrin, a type II ribosome inactivating protein from the Abrus precatorius plant, is extremely toxic. It has been shown to be 75 times more potent than its infamous sister toxin, ricin and their potential use in bio-warfare is a cause of major concern. Although several vaccine candidates are under clinical trials for ricin, none are available against abrin. The present study proposes a chimeric protein, comprising of 1-123 amino acids taken from the A chain of abrin and 124-175 amino acids from Abrus precatorius agglutinin A chain, as a vaccine candidate against abrin intoxication. The design was based on the inclusion of the immunogenic region of the full length protein and the minimal essential folding domains required for inducing neutralizing antibody response. The chimera also contains the epitope for the only two neutralizing antibodies; D6F10 and A7C4, reported against abrin till now. Active immunization with the chimera protected all the mice challenged with 45 X LD50of abrin. Also, passive transfer of antibodies raised against the chimera rescued all mice challenged with 50 X LD50of toxin. Hence the chimeric protein appears to be a promising vaccine candidate against abrin induced lethality.
authors.affiliation: Department of Biochemistry, Indian Institute of Science, Bangalore, Karnataka, 560012, India.
authors.forename: Vinita
authors.initials: V
authors.lastname: Tiwari
authors.affiliation: Department of Biochemistry, Indian Institute of Science, Bangalore, Karnataka, 560012, India.
authors.forename: Shradha
authors.initials: S
authors.lastname: Bagaria
authors.affiliation: Department of Biochemistry, Indian Institute of Science, Bangalore, Karnataka, 560012, India. Electronic address: anjali@biochem.iisc.ernet.in.
authors.forename: Anjali A
authors.initials: AA
authors.lastname: Karande
mesh_terms: D000036:Abrin / Q000235:genetics / Q000633:toxicity*; D029912:Abrus / Q000737:chemistry* / Q000276:immunology / Q000506:poisoning; D000373:Agglutinins / Q000276:immunology*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000235:genetics / Q000276:immunology; D000939:Epitopes; D005260:Female; D006801:Humans; D019169:Jurkat Cells; D008807:Mice, Inbred BALB C; D037121:Plant Lectins / Q000235:genetics / Q000276:immunology*; D010939:Plant Poisoning / Q000276:immunology / Q000517:prevention & control*; D011487:Protein Conformation; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology
chemical_list: D000373:Agglutinins; D057134:Antibodies, Neutralizing; D000939:Epitopes; D037121:Plant Lectins; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; C016940:abrus agglutinin; D000036:Abrin
keywords: Abrin; Abrus precatorius agglutinin; Chimeric protein; Ricin; Vaccine