Thermostable ricin vaccine protects rhesus macaques against aerosolized ricin

Epitope-specific neutralizing antibodies correlate with protection

Chad J. Roy, Robert N. Brey, Nicholas J. Mantis, Kelly Mapes, Iliodora V. Pop, Laurentiu M. Pop, Stephen Ruback, Stephanie Z. Killeen, Lara Doyle-Meyers, Heather S. Vinet-Oliphant, Peter J. Didier, Ellen S. Vitetta

Research output: Contribution to journalArticle

38 Citations (Scopus)

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 antibodies neutralized RT and competed to varying degrees with a panel of neutralizing and non-neutralizing mouse monoclonal antibodies known to recognize specific epitopes on native RTA. The resulting antibody competition profile could represent an immunologic signature of protection. Importantly, the same signature was observed using sera from RiVax-immunized humans.

Original languageEnglish (US)
Pages (from-to)3782-3787
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number12
DOIs
StatePublished - Mar 24 2015

Fingerprint

Ricin
Neutralizing Antibodies
Macaca mulatta
Epitopes
Vaccines
Antibodies
Castor Oil
Ricinus
United States Food and Drug Administration
Centers for Disease Control and Prevention (U.S.)
Aerosols
Aluminum
Galactose
Ribosomes
Fibrosis
Monoclonal Antibodies
Escherichia coli
Rabbits
Lung
Mutation

Keywords

  • Immunoprofiling
  • Monoclonal antibody
  • Rhesus macaques
  • Ricin
  • Vaccine

ASJC Scopus subject areas

  • General

Cite this

Thermostable ricin vaccine protects rhesus macaques against aerosolized ricin : Epitope-specific neutralizing antibodies correlate with protection. / Roy, Chad J.; Brey, Robert N.; Mantis, Nicholas J.; Mapes, Kelly; Pop, Iliodora V.; Pop, Laurentiu M.; Ruback, Stephen; Killeen, Stephanie Z.; Doyle-Meyers, Lara; Vinet-Oliphant, Heather S.; Didier, Peter J.; Vitetta, Ellen S.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 112, No. 12, 24.03.2015, p. 3782-3787.

Research output: Contribution to journalArticle

Roy, Chad J. ; Brey, Robert N. ; Mantis, Nicholas J. ; Mapes, Kelly ; Pop, Iliodora V. ; Pop, Laurentiu M. ; Ruback, Stephen ; Killeen, Stephanie Z. ; Doyle-Meyers, Lara ; Vinet-Oliphant, Heather S. ; Didier, Peter J. ; Vitetta, Ellen S. / Thermostable ricin vaccine protects rhesus macaques against aerosolized ricin : Epitope-specific neutralizing antibodies correlate with protection. In: Proceedings of the National Academy of Sciences of the United States of America. 2015 ; Vol. 112, No. 12. pp. 3782-3787.
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