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A randomized, placebo-controlled, blind anti-AIDS clinical trial: Safety and immunogenicity of a specific anti-IFNα immunization

par Gringeri, Alessandro;Barré-Sinoussi, Françoise Hélène F.;Lachgar, Abderrahim;Chams, Vida;Le Coq, H.;Fouchard, Michéle;Achour, Ammar;Fall, LS;Defer, Marie Christine;Picard, Odile;Hermans, Philippe ;Santagostino, Elena;Burny, Arsène ;Feldman, Michael;Chany, Charles;Zagury, Jean-François;Bizzini, Bernard;Zagury, Daniel;Mannucci, Pier Mannuccio M P.M.;Tradati, Filippo;Cultraro, D.;Buzzi, Anna Maria A.;Criscuolo, Marcelo;David, Annie;Guillemot, Laurent
Référence Journal of acquired immune deficiency syndromes, 7, 9, page (978-988)
Publication Publié, 1994

Article révisé par les pairs

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Résumé :

HIV-induced cytokine dysregulation, incluCling overproduction of the antiproliferative and cytolytic IFNα cytokine, represents a major component of the immune disorders characterizing AIDS. To block the overproduction of IFNα we designed an AIDS vaccine combination which included both an anti-HIV and/or an anti-IFNα immunization. The safety and immunogenicity of this multicomponent vaccine were tested in mice, Cercopithecus, two HIV noninfected individuals, and six HIV-1 seropositive immunocompromised patients enrolled in a 1-year open clinical trial. We now report the result of a 9-month short-term randomized, blind, placebo-controlled clinical trial (Phase I/II) performed in HIV-1 patients (22 individuals) to confirm safety/tolerance of the anti-IFNα vaccine and its immunogenicity and to evaluate whether the complex vaccine initially used could be simplified by removal of HIV compo-nent(s). Three groups of patients received inactivated IFNα (i-IFNα) associated with the immunomodulator P40 with HIV-1 antigens (groups B and C) or without (group A), and one group (D) was placebo. The clinical follow-up documented among those receiving i-IFNα showed that none developed AIDS and/or required antiretroviral chemotherapy. Viral load did not increase and CD4 cell count as well as cell-mediated immunity (CMI) stabilized or even significantly increased in group A. Immunogenicity of the preparations was determined by a positive delayed-type hypersensitivity (DTH) reaction to i-IFNα and the presence of serum antibodies to i-IFNα and to HIV-1 peptides, occurring only in treated patients. As previously planned, based on these safety data, the trial has been extended for an additional year and all patients were switched to protocol A (i-IFNα + P40). This second period of the trial, now open and ongoing, should allow us to evaluate further the innocuity of the i-IFNα preparation and whether anti-IFNα vaccine could provide a long-lasting CD4 cell count as well as CMI stabilization. © 1994 Raven Press Ltd., New York.