title: HIV-1 Tat-based vaccines: from basic science to clinical trials.
abstract: Vaccination against human immunodeficiency virus (HIV)-1 infection requires candidate antigen(s) (Ag) capable of inducing an effective, broad, and long-lasting immune response against HIV-1 despite mutation events leading to differences in virus clades. The HIV-1 Tat protein is more conserved than envelope proteins, is essential in the virus life cycle and is expressed very early upon virus entry. In addition, both humoral and cellular responses to Tat have been reported to correlate with a delayed progression to disease in both humans and monkeys. This suggested that Tat is an optimal target for vaccine development aimed at controlling virus replication and blocking disease onset. Here are reviewed the results of our studies including the effects of the Tat protein on monocyte-derived dendritic cells (MDDCs) that are key antigen-presenting cells (APCs), and the results from vaccination trials with both the Tat protein or tat DNA in monkeys. We provide evidence that the HIV-1 Tat protein is very efficiently taken up by MDDCs and promotes T helper (Th)-1 type immune responses against itself as well as other Ag. In addition, a Tat-based vaccine elicits an immune response capable of controlling primary infection of monkeys with the pathogenic SHIV89.6P at its early stages allowing the containment of virus spread. Based on these results and on data of Tat conservation and immune cross-recognition in field isolates from different clades, phase I clinical trials are being initiated in Italy for both preventive and therapeutic vaccination.
authors.affiliation: Laboratory of Virology, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Fanales-Belasio
authors.forename: Aurelio
authors.initials: A
authors.lastname: Cafaro
authors.forename: Andrea
authors.initials: A
authors.lastname: Cara
authors.forename: Donatella R M
authors.initials: DR
authors.lastname: Negri
authors.forename: Valeria
authors.initials: V
authors.lastname: Fiorelli
authors.forename: Stefano
authors.initials: S
authors.lastname: Butto
authors.forename: Sonia
authors.initials: S
authors.lastname: Moretti
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Maggiorella
authors.forename: Silvia
authors.initials: S
authors.lastname: Baroncelli
authors.forename: Zuleika
authors.initials: Z
authors.lastname: Michelini
authors.forename: Antonella
authors.initials: A
authors.lastname: Tripiciano
authors.forename: Leonardo
authors.initials: L
authors.lastname: Sernicola
authors.forename: Arianna
authors.initials: A
authors.lastname: Scoglio
authors.forename: Alessandra
authors.initials: A
authors.lastname: Borsetti
authors.forename: Barbara
authors.initials: B
authors.lastname: Ridolfi
authors.forename: Roberta
authors.initials: R
authors.lastname: Bona
authors.forename: Peter
authors.initials: P
authors.lastname: Ten Haaft
authors.forename: Iole
authors.initials: I
authors.lastname: Macchia
authors.forename: Pasqualina
authors.initials: P
authors.lastname: Leone
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Pavone-Cossut
authors.forename: Filomena
authors.initials: F
authors.lastname: Nappi
authors.forename: Eftyhia
authors.initials: E
authors.lastname: Vardas
authors.forename: Mauro
authors.initials: M
authors.lastname: Magnani
authors.forename: Elena
authors.initials: E
authors.lastname: Laguardia
authors.forename: Antonella
authors.initials: A
authors.lastname: Caputo
authors.forename: Fausto
authors.initials: F
authors.lastname: Titti
authors.forename: Barbara
authors.initials: B
authors.lastname: Ensoli
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002986:Clinical Trials as Topic; D015696:Gene Products, tat / Q000276:immunology* / Q000378:metabolism; D015497:HIV-1 / Q000276:immunology* / Q000378:metabolism; D008252:Macaca fascicularis; D013019:South Africa; D018417:Th1 Cells / Q000276:immunology; D014454:Uganda; D054322:tat Gene Products, Human Immunodeficiency Virus
chemical_list: D016915:AIDS Vaccines; D015696:Gene Products, tat; D054322:tat Gene Products, Human Immunodeficiency Virus