Abrogation of the antibenzylpenicilloyl (BPO) IgE response with BPO-polyvinyl alcohol conjugates.

Abstract

IgE antibodies to the benzylpenicilloyl (BPO) determinant and ovalbumin (OA) were readily induced B<sup>6</sup>D<sup>2</sup>F<sup>1</sup> mice by a single i.p. injection of 10 µg of BPO<sup>4</sup>-OA suspended with 1 mg AI(OH)<sup>3</sup> in 0.5 ml of saline. The potential of these mice to mount a <i>de novo</i> anti-BPO IgE antibody response was specifically abrogated by pretreatment of mice with tolerogenic conjugates consisting of the hapten coupled to the hydrophilic and nonimmunogenic polymers, polyvinyl alcohols (PVA), with average molecular weigths of 10,000 or 14,000 daltons. The average epitope density of these conjugates varied from 1.1 to 3.9. It is noteworthy that even BPO<sup>1.1</sup>-PVA, which elicied only weak PCA reactions in rats sensitized i.d. with mouse anti-BPO reaginic antibodies, was highly tolerogenic. More importantly, the ongoing anti-BPO reaginic response in sensitized mice was also readily suppressed by administration of these tolerogenic conjugates, e.g. a single dose of 100 µg of BPO<sup>2.7</sup>-PVA was sufficient to abolish an ongoing anti-BPO IgE response. Moreover, administration of these tolerogenic conjugates into mice sensitized to BPO<sup>4</sup>-OA, prior to their resensitization in presence of <i>Bordetella pertussis,</i> protected these animals from anaphylactic death on i.v. challenge with 2 mg of the polyvalent BPO<sup>9</sup>-MγG conjugate (MγG = mosue γ-globulins); by contrast, all control mice which had not received this tolerogenic regimen died of anaphylaxis. It is suggested that conjugates of PVA with haptenic antibiotic or other drug molecules may prove to be effective therapeutic agents for the specific suppression of IgE antibodies mediating allergies of the immediate type to a wide spectrum of low molecular weight allergenic compounds.