"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 occasionally overproduced. These cytokines could participate in the HIV-induced immunosuppression. To enable a HIV-infected organism to promote an immune reaction against the virus, the immune competence should tentatively 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 still immunogenic product, which we termed "kinoid", reminiscent of that of bacterial toxins which have been transformed into toxoids for vaccination. The "kinoid" derived from IFN alpha showed to be well tolerated and immunogenic, since its administration to experimental animals and humans should result in no untoward reactions, while eliciting the production of anti-IFN alpha antibodies. Active "kinoid" immunization should permit to counteract the overproduction of the corresponding cytokine when involved in pathogenesis. Another alternative, although less attractive than active anti-kinoid vaccination, is passive immunization by administering anti-kinoid antibodies. Biological antagonists of cytokine, as well as gene therapy should also be taken into consideration.