An active immunization approach to generate protective catalytic antibodies.
We report that mice immunized with a phosphate immunogen produced polyclonal 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 Michaelis-Menten kinetics in vitro with the following values at pH 8.0 and 25 degrees C: K(m) approximately 8.0 microM, k(cat)=4.8x10(-3)-5.8x10(-1), k(cat)/k(non-cat)=5.6x10(1)-6.8x10(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 PCAbs induced in vivo were also active in vivo, as immunization with the phosphate immunogen decreased the mouse blood concentration of carbaryl. To our knowledge, this is the first report demonstrating that active immunization generates antibodies possessing therapeutic catalytic function in vivo. We propose that active immunization schemes that induce enzymically active antibodies may provide a highly specific therapeutic approach for degrading toxic substances.
Wang
J
J
Department of Immunology, The University of Texas M.D. Anderson Cancer Center, Houston, 1515 Holcombe Blvd., TX 77030, USA.
Han
Y
Y
Wilkinson
M F
MF
D000818:Animals; D000906:Antibodies / Q000737:chemistry*; D017151:Antibodies, Catalytic / Q000737:chemistry*; D002384:Catalysis; D005260:Female; D006868:Hydrolysis; D007114:Immunization; D007074:Immunoglobulin G / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008956:Models, Chemical; D013997:Time Factors
D000906:Antibodies; D017151:Antibodies, Catalytic; D007074:Immunoglobulin G