title: A randomized, placebo-controlled, blind anti-AIDS clinical trial: safety and immunogenicity of a specific anti-IFN alpha immunization.
abstract: HIV-induced cytokine dysregulation, including overproduction of the antiproliferative and cytolytic IFN alpha cytokine, represents a major component of the immune disorders characterizing AIDS. To block the overproduction of IFN alpha we designed an AIDS vaccine combination which included both an anti-HIV and/or an anti-IFN alpha 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-IFN alpha vaccine and its immunogenicity and to evaluate whether the complex vaccine initially used could be simplified by removal of HIV component(s). Three groups of patients received inactivated IFN alpha (i-IFN alpha) 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-IFN-alpha 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-IFN alpha and the presence of serum antibodies to i-IFN alpha 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-IFN alpha+P40). This second period of the trial, now open and ongoing, should allow us to evaluate further the innocuity of the i-IFN alpha preparation and whether anti-IFN alpha vaccine could provide a long-lasting CD4 cell count as well as CMI stabilization.
authors.affiliation: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, IRCCS Maggiore Hospital, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Gringeri
authors.forename: E
authors.initials: E
authors.lastname: Santagostino
authors.forename: P M
authors.initials: PM
authors.lastname: Mannucci
authors.forename: F
authors.initials: F
authors.lastname: Tradati
authors.forename: D
authors.initials: D
authors.lastname: Cultraro
authors.forename: A
authors.initials: A
authors.lastname: Buzzi
authors.forename: M
authors.initials: M
authors.lastname: Criscuolo
authors.forename: A
authors.initials: A
authors.lastname: David
authors.forename: L
authors.initials: L
authors.lastname: Guillemot
authors.forename: F
authors.initials: F
authors.lastname: Barré-Sinoussi
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D015483:HIV Antibodies / Q000097:blood; D016655:HIV Core Protein p24 / Q000097:blood; D015658:HIV Infections / Q000628:therapy*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D006968:Hypersensitivity, Delayed; D007111:Immunity, Cellular; D016233:Immunotherapy, Active; D007273:Injections, Intramuscular; D016898:Interferon-alpha / Q000097:blood / Q000276:immunology*; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory; D014766:Viremia / Q000209:etiology
chemical_list: D016915:AIDS Vaccines; D015483:HIV Antibodies; D016655:HIV Core Protein p24; D016898:Interferon-alpha