STEPWISE IODINATION - A GENERAL PROCEDURE FOR DETOXIFICATION OF PROTEINS SUITABLE FOR VACCINE DEVELOPMENT AND ANTISERUM PRODUCTION

By gradual incorporation of stable iodine into toxins and whole venoms it is possible to abolish completely the lesion and lethal properties of the native components. Allergen extracts can be turned anallergic. Physiological proteins with strong biological activity can also be re ndered innocuous. Tyrosine and histidine are the reactive groups that incorporate the hapten. Within the same batch oi protein, there is a d efined ratio hapten/protein to achieve the desired modified properties of the derivative. The iodinating solutions are easily prepared, can be accurately standardized and have unlimited shelf lives. The derivat ives are obtained in a short time. The cost oi the entire procedure is very low. The method was applied to tityustoxin and whole venom of th e scorpion Tityus serrulatus; crotoxin and whole venom of Crotalus dur issus terrificus: to five bothropic venoms; to allergenic extracts of Schistosoma mansoni; to cholera and tetanus toxin; and to insulin, kal likrein and tonin. The derivatives obtained were stable, did not show any reversion to toxicity, generated antibodies against the native ant igens and gave active protection when injected into animals. No local or systemic side effects were observed, even alter prolonged use. The injections were also apparently painless. By extensive haptenization s elf proteins can be rendered non-self, able to generate antibodies aga inst both the derivative and the native unmodified protein, and iodina tion was very convenient for this purpose. A new schedule for immuniza tion, only feasible with completely toxoided venoms is presented. it i s based on a clonal expansion induced by a small dose, followed by an exponential saturation dose of the same toroid. The attainment of high er levels of antibodies against the native antigen, in the generated s era is unmatched by other procedures. (C) 1998 The International Assoc iation of Biological Standardization.