Are CD4 and Fas peptide identities of gp120 relevant to the molecular basis of AIDS pathogenesis? - A model for HIV1-induced immunopathogenesis

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Repair of the in vitro HIV-1-induced immunosuppression and blockade of the generation of functional suppressive CD8 cells by anti-alpha interferon and anti-Tat antibodies

The acute human immunodeficiency virus type 1 (HIV-1) infection of activated peripheral blood mononuclear cells (PBMCs) from normal donors results in inhibition of cell proliferation and generation of functional suppressive T cells. Cultured HIV-1 infected PBMCs but not uninfected PBMCs, following irradiation, can inhibit the proliferation of antigen-activated autologous T cells in a dose-dependent way. CD8' cell subpopulation is responsible for this inhibition. The presence of anti-alpha interferon (IFNα) and anti-Tat antibodies in the culture medium counteracts the HIV-1-induced immunosuppression and prevents the generation of suppressive T cells by these PBMCs. The reported data should have major implications for strategies of AIDS treatment which, in association with antiviral drugs, aim at targetting immune disorders.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Biological effect of active anti-IFNα immunization in HIV-infected patients

Circulating interferon (IFN) was investigated in HIV-1 seropositive patients by measuring the IFNα antiviral effect in the serum. While serum of healthy seronegative individuals exhibits an antiviral effect, not due to IFNs, considered as background, serum of seropositive patients showed an additional antiviral effect due to the abnormal presence of IFNα. Increased titers of IFNα were found in the course of the HIV infection and seemed to correlate with the evolution of AIDS disease. Furthermore, patients immunized against IFNα had both stabilized CD4 cell count and decreased IFNα in their serum. HIV-1-infected patients also exhibited higher titers of natural anti-IFN antibodies than seronegative controls and the level of specific antibodies (Abs) markedly increased in immunized patients. Finally, serum from immunized patients, when compared to seronegative controls, exhibits an interferon neutralizing capacity.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Absence of clinical, virological, and immunological signs of progression in HIV-1-infected patients receiving active anti-interferon-α immunization: A 30-month follow-up report

Twenty-seven HIV-1-infected patients, 16 at early stage of disease and without concomitant antiretroviral therapy and 11 at more advanced stage of disease receiving antiretroviral therapy, have been followed since their enrollment. November 1992 and July 1993, respectively, in phase I/II studies to evaluate safety and immunogenicity of an anti-interferon-α (IFN-α) vaccine, aimed at modulating the impaired cytokine network in AIDS patients by counteracting IFN-α overproduction. We compared clinical, virological, and immunological markers of disease progression, including circulating IFN- α levels in a 24- to 30-month follow-up period with those of 62 patients fulfilling the same enrollment criteria and comparable for sex, risk factor, and age, regularly followed at our center. Anti-IFN-α immunization consisted of four-six intramuscular injections 1 month apart of a water-in-oil emulsion of 500 μg formalin-inactivated recombinant IFN-α-2b (iIFN-α) followed by intramuscular injections of 250 μg iIFN-α adsorbed onto calcium phosphate every 3 months. Neither clinical deterioration nor a CD4+ cell count decrease from pretreatment values was observed in IFN-α-immunized patients in the follow-up period, whereas clinical and immunological disease progressions were observed among open-comparison patients. Furthermore, statistical analysis showed a strong association between occurrence of clinical manifestations and high circulating IFN-α titers, while nonprogression of IFN-α-immunized patients was associated with decreased levels of circulating IFN-α.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

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

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.SCOPUS: ar.jinfo:eu-repo/semantics/publishe