PROTECTION AGAINST ALPHA-BUNGAROTOXIN POISONING BY IMMUNIZATION WITH SYNTHETIC TOXIN PEPTIDES

The purpose of the present work was to determine the ability of BgTX p eptides, corresponding to the various loops and exposed regions of alp ha-bungarotoxin (BgTX) and representing regions that are recognized by B and/or T cells, to stimulate protective immunity in mice against in vivo challenge with BgTX. The BgTX LD(50) values in non-immune mice o r mice that had been immunized with proteins and peptides unrelated to BgTX were: Balb/c, 0.128 mu g/g; SJL, 0.156 mu g/g. Immunization of B alb/c and SJL mice with each of the synthetic peptides in its free for m afforded considerable protection against BgTX poisoning. Peptides L1 (residues 3-16), L2 (residues 26-41) and C-tail (residues 66-74) of B gTX were the most protective and mice immunized with these peptides su rvived LD(50) values that were three times higher than control mice. I mmunization with an equimolar mixture of the three peptides was even m ore protective and these mice survived even higher challenge doses of BgTX (4.6-fold higher than LD(50) of controls; i.e. protection index, PI=4.6). An OVA conjugate carrying all three peptides, when used as an immunogen, conferred extremely high protection (PI greater than or eq ual to 18.1) which was almost double the protection obtained by BgTX i mmunization (PI=9.7). Thus, the conjugate of the three peptides should serve as an effective vaccine against BgTX poisoning. Furthermore, th ese results with BgTX peptides should serve as a prototype for the des ign and synthesis of peptide vaccines against other members of this la rge family of toxins which include both long and short neurotoxins as well as cytotoxins. Copyright (C) 1996 Elsevier Science Ltd.