Toxicity and Efficacy Evaluation of Soluble Recombinant Ricin Vaccine

• Published in: Vaccines (Basel) Vol. 12; no. 10; p. 1116
• Main Authors: Yun, Hyeongseok, Joe, Hae Eun, Song, Dong Hyun, Song, Young-Jo, Hong, Sunghyun, Kim, Chang-Hwan, Kim, Na Young, Hur, Gyeung Haeng, Yu, Chi Ho
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 29.09.2024
• Subjects: Amino acids; Animals; Chemical bonds; Clinical trials; E coli; Edema; Glycosidases; Mutation; N-glycosidase; Pets; plant toxin; Protein biosynthesis; Protein expression; Protein folding; Protein synthesis; Proteins; R51-3; Rabbits; Ribosome-inactivating protein; Ricin; ricin vaccine; RNA N-glycosidase; rRNA; Toxicity; Toxicity testing; Toxins; Transcription; Vaccine development; Vaccines; Vascular leak syndrome; United States > US; South Korea; R51-3; plant toxin; ricin vaccine; ricin
• ISSN: 2076-393X; 2076-393X
• DOI: 10.3390/vaccines12101116

Ricin, a toxin extracted from the seeds of , is classified as a ribosome-inactivating protein. The A-subunit of ricin shows RNA -glycosidase activity that cleaves ribosomal RNA (rRNA) and exhibits toxicity by inhibiting protein synthesis and inducing vascular leak syndrome. In this study, we created a truncated version of the previously developed R51 ricin vaccine (RTA 1-194 D75C Y80C) through in silico analysis. The resulting R51-3 vaccine showed a more-than-six-fold increase in soluble protein expression when compared to R51, with over 85% solubility. In a pilot toxicity test, no toxicity was observed in hematological and biochemical parameters in BALB/c mice and New Zealand white rabbits following five repeated administrations of R51-3. Furthermore, R51-3 successfully protected mice and rabbits from a 20 × LD ricin challenge after three intramuscular injections spaced 2 weeks apart. Similarly, monkeys that received three injections of R51-3 survived a 60 µg/kg ricin challenge. These findings support R51-3 as a promising candidate antigen for ricin vaccine development.