Thermostable ricin vaccine protects XXXX against aerosolized ricin: Epitope-specific neutralizing antibodies correlate with protection.

@entity1 @entity3775 @entity82 @entity9377 @entity526 @entity19 @entity71336 @entity95 @entity11849 @entity358 @entity3649 @entity2608 @entity204 @entity71337
UNASSIGNED: @entity11849 ( @entity11849 ) is the second most lethal toxin known; it has been designated by the CDC as a select agent. @entity11849 is made by the @entity9377 plant; an estimated 50,000 tons of @entity11849 are produced annually as a by-product of castor oil. @entity11849 has two subunits, a ribotoxic A chain (RTA) and @entity3649 -binding B chain (RTB). @entity11849 binds to all @entity1 cells and once internalized, a single RTA catalytically inactivates all of the ribosomes in a cell. Administered as an aerosol, @entity11849 causes rapid @entity358 and @entity82 followed by @entity204 . 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 @entity71336 / @entity71337 (RiVax). The protein is expressed in @entity526 and is nontoxic and immunogenic in @entity19 , @entity95 , and @entity1 . When vaccinated @entity19 are challenged with injected, aerosolized, or orally administered (gavaged) @entity11849 , they are completely protected. We have now developed a thermostable, @entity3775 -adjuvant-containing formulation of RiVax and tested it in @entity2608 . After three injections, the animals developed antibodies that completely protected them from a lethal dose of aerosolized @entity11849 . These antibodies neutralized @entity11849 and competed to varying degrees with a panel of neutralizing and nonneutralizing 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 @entity1 .
