An active immunization approach to generate protective catalytic antibodies

We report that mice immunized with a phosphate immunogen produced polyclona l catalytic antibodies (PCAbs) that catalysed the hydrolysis of carbaryl, a widely used broad-spectrum carbamate insecticide that exerts toxic effects in animals and humans. The reaction catalysed by the PCAbs (IgGs) obeyed M ichaelis-Menten kinetics in vitro with the following values at pH 8.0 and 2 5 degreesC: K-m approximate to 8.0 muM, k(eat) = 4.8 x 10(-3)-5.8 x 10(-1), k(cat)/k(non-cat) = 5.6 x 10(1)-6.8 x 10(3) (where k(non-cat) is the rate constant of the reaction in the absence of added catalyst). The PCAbs were also active in whole sera under physiological conditions in vitro. The PCAb s induced in vivo were also active in vivo, as immunization with the phosph ate immunogen decreased the mouse blood concentration of carbaryl. To our k nowledge, this is the first report demonstrating that active immunization g enerates antibodies possessing therapeutic catalytic function in vivo. We p ropose that active immunization schemes that induce enzymically active anti bodies may provide a highly specific therapeutic approach for degrading tox ic substances.