Isolation of a human-like antibody fragment ( XXXX ) that neutralizes ricin biological activity.

@entity1 @entity1522 @entity9377 @entity5434 @entity10389 @entity10390
BACKGROUND: Ricin is a lethal toxin that inhibits protein synthesis. It is easily extracted from a ubiquitously grown plant, @entity9377 , and thus readily available for use as a bioweapon (BW). Anti-ricin antibodies provide the only known therapeutic against ricin intoxication. RESULTS: In this study, after immunizing a non- @entity1 primate ( @entity5434 ) with the ricin chain A (RTA), a phage-displayed immune library was built (2 x 108 clones), that included the lambda light chain fragment. The library was screened against ricin, and specific binders were sequenced and further analyzed. The best clone, 43RCA, was isolated using a new, stringent neutralization test. 43RCA had a high, picomolar affinity (41 pM) and neutralized ricin efficiently (IC50 = 23 +/- 3 ng/ml, corresponding to a [ @entity10390 ]/[ricin] molar ratio of 4). The neutralization capacity of 43RCA compared favourably with that of polyclonal anti-deglycosylated A chain (anti-dgRCA) IgGs, obtained from hyperimmune mouse serum, which were more efficient than any monoclonal at our disposal. The 43RCA sequence is very similar to that for human IgG germline genes, with 162 of 180 identical @entity1522 for the VH and @entity10389 (90% sequence identity). CONCLUSION: Results of the characterization studies, and the high degree of identity with @entity1 germline genes, altogether make this anti-ricin @entity10390 , or an IgG derived from it, a likely candidate for use in @entity1 to minimize effects caused by ricin intoxication.
