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

Aurelio Cafaro, Antonella Tripiciano, Cecilia Sgadari, Stefania Bellino, Orietta Picconi, Olimpia Longo, Vittorio Francavilla, Stefano Buttò, Fausto Titti, Paolo Monini, Fabrizio Ensoli, Barbara Ensoli

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)S13-S29
JournalExpert Opinion on Biological Therapy
Volume15
DOIs
Publication statusPublished - 2015

Keywords

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

ASJC Scopus subject areas

  • Medicine(all)

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    Cafaro, A., Tripiciano, A., Sgadari, C., Bellino, S., Picconi, O., Longo, O., Francavilla, V., Buttò, S., Titti, F., Monini, P., Ensoli, F., & Ensoli, B. (2015). Development of a novel AIDS vaccine: the HIV-1 transactivator of transcription protein vaccine. Expert Opinion on Biological Therapy, 15, S13-S29. https://doi.org/10.1517/14712598.2015.1021328