Polyclonal catalytic antibodies.

ABSTRACT

Polyclonal catalytic antibodies offer advantages in the evaluation of immunogens and in the ease of production of large quantities of antibodies. They comprise the entire immune response of an animal to an immunogen where monoclonals represent a subset. Polyclonal antibodies are consequently particularly suitable for evaluating catalytic antibody responses generated by different haptens or a group of structurally related haptens. The authors reported the first polyclonal catalytic antibodies in 1990. An unexpected finding is that polyclonal catalytic antibodies show single-site kinetic behaviour, i.e. whatever structural heterogeneity exists, the kinetic behaviour is homogeneous. Many groups worldwide have since published work in this area. Three groups are prominent. The authors' group, a group based in Austin, Texas, and led by Iverson, and a Shanghai group. The authors' group works with sheep antibodies and has published mechanistic studies and, more recently, specificity studies that revealed the catalysis of a beta-lactam. Most of this work over a 10-year period was performed by using a single bleed from a single sheep, which gives an indication of the ease of production and utility of such catalytic antibodies. Iverson's group works with rabbit antibodies and has published much work on the evaluation of catalytic antibodies generated by structurally related haptens. The Shanghai group has concentrated on the studies of polyclonal catalytic antibodies for electrocyclic reactions where any danger of contaminating enzymes is reduced. The use of immunisation to generate therapeutically useful catalytic antibodies (necessarily polyclonal) in a host animal is an attractive target. Several groups are working towards this. The authors themselves have published in this area and promising recent studies come from a group working in France on immunisation to protect against nerve agents and a Texas group (based in Houston) that has demonstrated active immunisation to generate antibodies that catalyse the hydrolysis of a carbamate insecticide.