HIV-1 Tat-based vaccines: from basic science to clinical trials.
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.
Fanales-Belasio
Emanuele
E
Laboratory of Virology, Istituto Superiore di Sanità, Rome, Italy.
Cafaro
Aurelio
A
Cara
Andrea
A
Negri
Donatella R M
DR
Fiorelli
Valeria
V
Butto
Stefano
S
Moretti
Sonia
S
Maggiorella
Maria Teresa
MT
Baroncelli
Silvia
S
Michelini
Zuleika
Z
Tripiciano
Antonella
A
Sernicola
Leonardo
L
Scoglio
Arianna
A
Borsetti
Alessandra
A
Ridolfi
Barbara
B
Bona
Roberta
R
Ten Haaft
Peter
P
Macchia
Iole
I
Leone
Pasqualina
P
Pavone-Cossut
Maria Rosaria
MR
Nappi
Filomena
F
Vardas
Eftyhia
E
Magnani
Mauro
M
Laguardia
Elena
E
Caputo
Antonella
A
Titti
Fausto
F
Ensoli
Barbara
B
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
D016915:AIDS Vaccines; D015696:Gene Products, tat; D054322:tat Gene Products, Human Immunodeficiency Virus