Phase I Safety and Immunogenicity Preventative Vaccine Trial Based on Recombinant Tat Protein — ISSP-001  

HIV Infections Clinical Trial

Official title: A Phase I Safety and Immunogenicity Trial of Recombinant HIV-1 Tat Protein in HIV-1 Uninfected Adult Volunteers

Status Completed

Clinical Trial Summary

This Phase I study is directed at evaluating the safety profile (as a primary end-point) and the immunogenicity (as a secondary end-point) of the recombinant HIV-1 Tat vaccine in healthy, immunologically competent adult subjects without identifiable risk of HIV-1 infection.

Clinical Trial Description

The development of a vaccine against HIV/AIDS has been primary focused on the structural proteins (Env, Gag) of HIV-1 with the aim of inducing sterilizing immunity by blocking virus entry. Alternative approaches are focused on new vaccine strategies aimed at modifying the virus-host dynamic favouring the establishment of a long-term non-progressing disease status. Such strategies target regulatory proteins that are the first to be expressed after infection and are essential for viral replication, infectivity and pathogenesis. Thus, this approach may be effective for both preventive and therapeutic vaccination strategies.

Being a very early viral regulatory protein necessary for viral gene expression, cell-to-cell virus transmission and disease progression, Tat represents a key target protein for the host immune response and an optimal candidate for such a vaccination strategy.

Preclinical studies demonstrated that vaccination with a biologically active Tat protein is safe, elicits a broad and specific immune response and induces a long-term protection against infection. Cross-sectional and longitudinal studies in natural infection suggest that the presence of an anti-Tat humoral immune response correlates with asymptomatic infection and with a slower disease progression while the presence of CD8+ T cell responses to Tat correlate with early virus control both in humans and monkeys. Since the immunogenic regions of Tat are well conserved among the HIV-1 M group, a vaccine based on Tat may be used in different geographic areas of the world.

The subjects were stratified in two Arms according to the administration route to receive 5 intradermal or subcutaneous immunizations at 4 weeks intervals. ;

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Prevention

Related Conditions & MeSH terms

• HIV Infections

• NCT number: NCT00529698
• Study type: Interventional
• Source: Istituto Superiore di Sanità
• Status: Completed
• Phase: Phase 1
• Start date: January 2004
• Completion date: November 2007