KINOIDS - THE BASIS FOR ANTICYTOKINE IMMUNIZATION AND THEIR USE IN HIV-INFECTION

HIV infection is characterized, at least in part, by the dysregulation of the cytokine network. Both IFN gamma and IFN alpha are occasionall y overproduced. These cytokines could participate in the HIV-induced i mmunosuppression. To enable a HIV-infected organism to promote an immu ne reaction against the virus, the immune competence should tentativel y be restored by counteracting the overproduction of IFN alpha because of its well known antiproliferative properties. For this purpose, IFN alpha was chemically converted into a biologically inactive, but stil l immunogenic product, which we termed ''kinoid'', reminiscent of that of bacterial toxins which have been transformed into toxoids for vacc ination. The ''kinoid'' derived from IFN alpha showed to be well toler ated and immunogenic, since its administration to experimental animals and humans should result in no untoward reactions, while eliciting th e production of anti-IFN alpha antibodies. Active ''kinoid'' immunizat ion should permit ct to counteract the overproduction of the correspon ding cytokine when involved in pathogenesis. Another alternative, alth ough less attractive than active anti-kinoid vaccination, is passive i mmunization by administering anti-kinoid antibodies. Biological antago nists of cytokine, as well as gene therapy should also be taken into c onsideration.