Tat toxoid as a component of a preventive vaccine in seronegative subjects.
Because administration of Tat protein, the HIV-1 toxin that induces immunosuppression and apoptosis, may be deleterious to the host immune system, a chemically inactivated but nonetheless immunogenic Tat preparation, Tat toxoid, was used to immunize seronegative individuals against Tat. In an open, controlled, phase I clinical trial, Tat toxoid turned out to be safe, well tolerated, and able to trigger a specific immune reaction. In particular, a threefold to more than 10-fold increase of circulating antibodies directed against the native Tat was observed after immunization in all of 5 immunized study subjects, together with a positive reaction to delayed-type hypersensitivity (DTH) skin test with Tat toxoid in vivo and increased lymphoproliferative response to native Tat in vitro. Persistent (> or =1 year) high levels of circulating anti-Tat antibodies could prevent the Tat-induced immune suppression and, following HIV-1 exposure, allow the anti-HIV-1 cellular immune response, with its early release of protective beta-chemokines, to occur leading to an increase of host resistance, that is, protection.
Gringeri
A
A
A. Bianchi Bonomi Hemophilia and Thrombosis Center, Istituto di Ricovero e Cura a Carattere Scientifico Maggiore Hospital and State University of Milan, Italy. hemophilia_ctr@polic.cilea.it
Santagostino
E
E
Muça-Perja
M
M
Le Buanec
H
H
Bizzini
B
B
Lachgar
A
A
Zagury
J F
JF
Rappaport
J
J
Burny
A
A
Gallo
R C
RC
Zagury
D
D
D016915:AIDS Vaccines / Q000276:immunology*; D000328:Adult; D000917:Antibody Formation; D003257:Consumer Product Safety; D004361:Drug Tolerance; D005260:Female; D015696:Gene Products, tat / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D008297:Male; D008875:Middle Aged; D011993:Recombinant Fusion Proteins / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology*
D016915:AIDS Vaccines; D015696:Gene Products, tat; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic