TY - JOUR
T1 - A randomized, placebo-controlled, blind anti-AIDS clinical trial
T2 - Safety and immunogenicity of a specific anti-IFNα immunization
AU - Gringeri, A.
AU - Santagostino, E.
AU - Mannucci, P. M.
AU - Tradati, F.
AU - Cultraro, D.
AU - Buzzi, A.
AU - Criscuolo, M.
AU - David, A.
AU - Guillemot, L.
AU - Barré-Sinoussi, F.
AU - Lachgar, A.
AU - Chams, V.
AU - Le Coq, H.
AU - Fouchard, M.
AU - Achour, A.
AU - Fall, L.
AU - Defer, M. C.
AU - Picard, O.
AU - Hermans, P.
AU - Burny, A.
AU - Feldman, M.
AU - Chany, C.
AU - Zagury, J. F.
AU - Bizzini, B.
AU - Zagury, D.
PY - 1994
Y1 - 1994
N2 - 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.
AB - 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.
KW - AIDS clinical trial
KW - Anti-cytokine vaccination
KW - Anti-IFNα immunization
KW - HIV-1-Interfer-on-α
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M3 - Article
C2 - 7914235
AN - SCOPUS:0028170090
VL - 7
SP - 978
EP - 988
JO - Journal of Acquired Immune Deficiency Syndromes
JF - Journal of Acquired Immune Deficiency Syndromes
SN - 1525-4135
IS - 9
ER -