Tat toxoid as a component of a preventive vaccine in seronegative subjects

Because administration of Tat protein, the HIV-I toxin that induces immunos uppression and apoptosis, may be deleterious to the host immune system, a c hemically inactivated but nonetheless immunogenic Tat preparation, Tat toro id, was used to immunize seronegative individuals against Tar. In an open, controlled, phase I clinical trial, Tat toroid turned out to be safe, well tolerated, and able to trigger a specific immune reaction. In particular, a threefold to more than 10-fold increase of circulating antibodies directed against the native Tat was observed after immunization in all of 5 immuniz ed study subjects, together with a positive reaction to delayed-type hypers ensitivity (DTH) skin test with Tat toroid in vivo and increased lymphoprol iferative response to native Tat in vitro. Persistent (greater than or equa l to 1 year) high levels of circulating anti-Tat antibodies could prevent t he Tat-induced immune suppression and, following HN-I exposure, allow the a nti-HN-l cellular immune response, with its early release of protective bet a-chemokines, to occur leading to an increase of host resistance, that is, protection.