Thermostable ricin vaccine protects rhesus macaques against aerosolized ricin: Epitope-specific neutralizing antibodies correlate with protection

Proceedings of the National Academy of Sciences of the United States of America
Chad J RoyEllen S Vitetta

Abstract

Ricin toxin (RT) is the second most lethal toxin known; it has been designated by the CDC as a select agent. RT is made by the castor bean plant; an estimated 50,000 tons of RT are produced annually as a by-product of castor oil. RT has two subunits, a ribotoxic A chain (RTA) and galactose-binding B chain (RTB). RT binds to all mammalian cells and once internalized, a single RTA catalytically inactivates all of the ribosomes in a cell. Administered as an aerosol, RT causes rapid lung damage and fibrosis followed by death. There are no Food and Drug Administration-approved vaccines and treatments are only effective in the first few hours after exposure. We have developed a recombinant RTA vaccine that has two mutations V76M/Y80A (RiVax). The protein is expressed in Escherichia coli and is nontoxic and immunogenic in mice, rabbits, and humans. When vaccinated mice are challenged with injected, aerosolized, or orally administered (gavaged) RT, they are completely protected. We have now developed a thermostable, aluminum-adjuvant-containing formulation of RiVax and tested it in rhesus macaques. After three injections, the animals developed antibodies that completely protected them from a lethal dose of aerosolized RT. These antibod...Continue Reading

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Citations

Jan 27, 2016·Human Vaccines & Immunotherapeutics·Robert N BreyChad J Roy
Nov 12, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Deborah A SarkesDimitra N Stratis-Cullum
Jan 10, 2017·Disease Models & Mechanisms·Shahaf KatalanChanoch Kronman
Oct 20, 2017·Clinical and Vaccine Immunology : CVI·Madison Zuverink, Joseph T Barbieri
Jul 29, 2016·Clinical and Vaccine Immunology : CVI·Greta Van SlykeNicholas J Mantis
Jul 30, 2020·Annals of the New York Academy of Sciences·Jared RadbelHoward M Kipen
Mar 22, 2016·Expert Review of Vaccines·David J Vance, Nicholas J Mantis
Feb 19, 2019·Antibodies·Siva Krishna AngalakurthiNicholas J Mantis
Dec 3, 2016·The Journal of Biological Chemistry·Michael J RudolphNicholas J Mantis
Sep 22, 2015·Plant Biotechnology Journal·Stephen J StreatfieldVidadi Yusibov
Aug 23, 2016·Expert Opinion on Drug Delivery·Susan A ShorterSimon C W Richardson
Jan 11, 2019·JCI Insight·Chad J RoyNicholas J Mantis
Jul 18, 2019·Journal of Leukocyte Biology·Bridget MooneyNicholas J Mantis
Mar 17, 2021·Expert Review of Vaccines·Yizhi Qi, Christopher B Fox
Feb 13, 2016·EBioMedicine·Karen A O MartinsSina Bavari
Oct 13, 2020·Neurologic Clinics·James J Sejvar
Feb 23, 2019·Toxicon : Official Journal of the International Society on Toxinology·Igo Renan Albuquerque de AndradeAntonio Silvio do Egito

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