title: Development of a novel AIDS vaccine: the HIV-1 transactivator of transcription protein vaccine.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Istituto Superiore di Sanità, National AIDS Center , Rome , Italy barbara.ensoli@iss.it.
authors.forename: Aurelio
authors.initials: A
authors.lastname: Cafaro
authors.forename: Antonella
authors.initials: A
authors.lastname: Tripiciano
authors.forename: Cecilia
authors.initials: C
authors.lastname: Sgadari
authors.forename: Stefania
authors.initials: S
authors.lastname: Bellino
authors.forename: Orietta
authors.initials: O
authors.lastname: Picconi
authors.forename: Olimpia
authors.initials: O
authors.lastname: Longo
authors.forename: Vittorio
authors.initials: V
authors.lastname: Francavilla
authors.forename: Stefano
authors.initials: S
authors.lastname: Buttò
authors.forename: Fausto
authors.initials: F
authors.lastname: Titti
authors.forename: Paolo
authors.initials: P
authors.lastname: Monini
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Ensoli
authors.forename: Barbara
authors.initials: B
authors.lastname: Ensoli
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology / Q000627:therapeutic use*; D000818:Animals; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D002986:Clinical Trials as Topic / Q000379:methods; D018450:Disease Progression; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000276:immunology / Q000627:therapeutic use*
chemical_list: D016915:AIDS Vaccines; D054322:tat Gene Products, Human Immunodeficiency Virus
keywords: HAART intensification; HIV-1 eradication; HIV-1 therapeutic vaccine; neutralization Tat