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

A. Gringeri, E. Santagostino, P. M. Mannucci, F. Tradati, D. Cultraro, A. Buzzi, M. Criscuolo, A. David, L. Guillemot, F. Barré-Sinoussi, A. Lachgar, V. Chams, H. Le Coq, M. Fouchard, A. Achour, L. Fall, M. C. Defer, O. Picard, P. Hermans, A. BurnyM. Feldman, C. Chany, J. F. Zagury, B. Bizzini, D. Zagury

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)978-988
Number of pages11
JournalJournal of Acquired Immune Deficiency Syndromes
Volume7
Issue number9
Publication statusPublished - 1994

Keywords

  • AIDS clinical trial
  • Anti-cytokine vaccination
  • Anti-IFNα immunization
  • HIV-1-Interfer-on-α

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)
  • Virology
  • Immunology and Allergy

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