Targeting Tat and IFN(alpha) as a therapeutic AIDS vaccine

Evolution to AIDS is characterized by a progressive cellular immune suppression. Although there is substantial evidence for several mechanisms involved in disrupting the immune response by induction of apoptosis in responder cells by contact with infected cells, we propose that humoral factors also play a role, and that one such factor is the extracellular form of the human immunodeficiency virus (HIV)-1 Tat protein and another is IFN(alpha). Both Tat and interferon-alpha (IFN(alpha)) inhibit antigen-stimulate T-cell proliferation, and specific anti-Tat and/or anti-IFN(alpha) Abs prevent generation of HIV-1-induced suppressor cells. We propose that high titer anti-Tat and/or anti-IFN(alpha) Abs, neutralizing extracellular Tat, and/or IFN(alpha), induced by vaccines described here, antagonize HIV-1-induced immunosuppression. Innocuous vaccines were prepared by using inactivated but immunogenic Tat (Toxoid) and inactivated and immunogenic IFN(alpha) (kinoid) derivatives. Both Tat Toxoid and IFN(alpha) kinoid were well tolerated and elicited specific neutralizing antibodies (Abs) in mice, monkeys, and seronegative and HIV-1-infected individuals.