PRECLINICAL ASSESSMENT OF IMMUNOREACTIVITY OF A NEW PURIFIED EQUINE F(AB')(2) AGAINST EUROPEAN VIPER VENOM

The immunological and pharmacokinetic properties of a new, further pur ified, pasteurized preparation of equine F(ab')(2) (VIPERFAV) against Vipera aspis, Vipera berus, and Vipera ammodytes venom were compared w ith the current equine F(ab')2 preparation (IPSER Europe). Affinity co nstants of the V. aspis-specific F(ab')(2) were determined using biose nsor technology and found to be in the range of 10(8) M-1 for the four antigenic fractions of V, aspis toxins and for both F(ab')(2) prepara tions. The improvement of 51% in the specific activity (LD50 mg(-1)) o f the new F(ab')(2) was in close agreement with the 1.8-fold increase in the immunoreactive fraction of the new preparation. In vivo investi gations of venom immunocomplexation by F(ab')(2) in rabbits confirmed the ability of F(ab')(2) to neutralize and redistribute toxin venom. I nfusion of a stoichiometric molar ratio (i.e., 1 mg kg(-1)) of the new antivenom induced a 2.3-fold elevation of the plasma venom concentrat ion with a T-max observed 8 h after F(ab')(2) administration and a dec line in the terminal half-life from 31.92 +/- 4.49 h to 16.73 +/- 4.34 h, in contrast, for the venom alone. The area under the curve was 1.4 -fold greater in the VIPERFAV group than in the IPSER Europe group dur ing the post-F(ab')(2) infusion period. Increasing the F(ab')(2) dose to 3 mg kg(-1) increased by 27% the percent of venom bound to F(ab')(2 ). Finally, the greater the venom distribution, the smaller and less p ronounced the plasma redistribution. These results demonstrate that th e purification and pasteurization steps involved in the preparation of the new F(ab')(2) have no deleterious influence on F(ab')(2) affinity but, on tile contrary, improve the protective efficacy. Alteration of viper venom kinetics by specific F(ab')(2) antivenom was also shown t o be dependent on the interval between of F(ab')(2) administration and venom bite and on the specific F(ab')(2) dose administered.