Tat Toxoid as a Component of a Preventive Vaccine in Seronegative Subjects

Abstract

Because administration of Tat protein, the HIV-1 toxin that induces immunosuppression and apoptosis, may be deleterious to the host immune system, a chemically inactivated but nonetheless immunogenic Tat preparation, Tat toxoid, was used to immunize seronegative individuals against Tat. In an open, controlled, phase I clinical trial, Tat toxoid 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 immunized study subjects, together with a positive reaction to delayed-type hypersensitivity (DTH) skin test with Tat toxoid in vivo and increased lymphoproliferative response to native Tat in vitro. Persistent (> or =1 year) high levels of circulating anti-Tat antibodies could prevent the Tat-induced immune suppression and, following HIV-1 exposure, allow the anti-HIV-1 cellular immune response, with its early release of protective beta-chemokines, to occur leading to an increase of host resistance, that is, protection.

Vaccination with Tat toxoid attenuates disease in simian/HIV-challenged macaques

“…A vaccine strategy that includes Tat toxoid (1,(30)(31)(32) and aims to reduce virus burden and AIDS pathogenesis is supported by our results. However, we do not support the idea that Tat vaccines and, especially, formulations containing native Tat will be effective as preventive, monovalent vaccines against HIV infection.…”

Transactivator of Transcription from HIV Type 1 Subtype E Selectively Inhibits TNF Gene Expression via Interference with Chromatin Remodeling of the TNF Locus

“…For example, Tat from subtype B has been studied as a potential vaccine by a number of groups (51)(52)(53)(54) and has shown excellent safety profiles in clinical phase I and II trials (55,56). Results obtained in monkey experiments using Tat as a vaccine demonstrated some protection against infectious challenge with SHIV (52)(53)(54)57).…”

The HIV-1 regulatory proteins Tat and Rev are frequently targeted by cytotoxic T lymphocytes derived from HIV-1-infected individuals

“…Effector-to-target ratio for all assays was 20:1. (38) and an HIV-1 Revcontaining DNA vaccine have been performed. The use of overlapping peptides in the ELISPOT assays indicates that there are multiple epitopes in Tat and Rev, three of which are optimally defined.…”