Development of a novel AIDS vaccine: the HIV-1 transactivator of transcription protein vaccine

Abstract

Introduction: Classical approaches aimed at targeting the HIV-1 envelope as well as other structural viral proteins have largely failed. The HIV-1 transactivator of transcription (Tat) is a key HIV virulence factor, which plays pivotal roles in virus gene expression, replication, transmission and disease progression. Notably, anti-Tat Abs are uncommon in natural infection and, when present, correlate with the asymptomatic state and lead to lower or no disease progression. Hence, targeting Tat represents a pathogenesis-driven intervention.

Areas covered: Here, we review the rationale and the translational development of a therapeutic vaccine targeting the Tat protein. Preclinical and Phase I studies, Phase II trials with Tat in anti-Tat Ab-negative, virologically suppressed highly active antiretroviral therapy-treated subjects in Italy and South Africa were conducted. The results indicate that Tat-induced immune responses are necessary to restore immune homeostasis, to block the replenishment and to reduce the size of the viral reservoir. Additionally, they may help in establishing key parameters for highly active antiretroviral therapy intensification and a functional cure.

Expert opinion: We propose the therapeutic setting as the most feasible to speed up the testing and comparison of preventative vaccine candidates, as the distinction lies in the use of the vaccine in uninfected versus infected subjects and not in the vaccine formulation.

Keywords:

• HAART intensification
• HIV-1 eradication
• HIV-1 therapeutic vaccine
• neutralization Tat

Acknowledgments

The authors thank MT Maggiorella, L Sernicola, MR Pavone Cossut, B Collacchi, S Moretti, F Ferrantelli, A Scoglio, MJ Ruiz Alvarez, C Ariola, M Campagna, F Stivali (National AIDS Center, Istituto Superiore di Sanità, and Pathology and Microbiology, San Gallicano Hospital, ‘Istituti Fisioterapici Ospitalieri’, Rome, Italy) for laboratory support; and F Cammisa and G Fornari Luswergh (National AIDS Center, Istituto Superiore di Sanità, Rome, Italy) for support to study management and editorial assistance, respectively; S De Menna, A Biondi, S Tobelli and F Fedeli (National AIDS Center, Istituto Superiore di Sanità, Rome, Italy) for administrative support.

Declaration of interest

This paper is part of a supplemental issue, sponsored by SciClone. The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents, received or pending, or royalties.

Notes

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