Neutralizing anti-Tat antibodies prolonged HAART interruption in vaccines in a prospective structured interruption study

Anti-Tat therapeutic vaccination has been clinically investigated by different groups [1-4], given that 1) extracellular Tat protein induces T cell apoptosis and cellular immune suppression, 2) epidemiological data showed that LTNP exhibit high level of serum anti-Tat Ab, negatively correlated with p24 antigenemia, 3) in Tat immunized macaques, viremia decreased following SHIV challenge. Anti-Tat therapeutic vaccination using Tat Toxoid adjuvanted either with Seppic [1,2] or with alum or DcChol (Aventis Pasteur) proved to be safe. A prospective structured treatment interruption study (STI) monitored according to EU guidelines was conducted at Hospital St-Pierre, Brussels (Pr. N. Clumeck) on 31 vaccinees who received a DcChol adjuvanted Tat Toxoid (n = 12), a DcChol placebo (n = 8) or non adjuvanted Tat toxoid (n = 11). The 2 year study follow-up showed that vaccinees developing high titer of Abs neutralizing Tat bioactivity prolonged HAART-interruption.info:eu-repo/semantics/publishedOral presentation. From 2006 International Meeting of The Institute of Human VirologyBaltimore, USA. 17–21 November, 200

Lectin production by human T-lymphocytes

Cultured human peripheral blood monocytes (PBMC) and the cell line H9 release a lectin. This lectin is not the previously described sarcolectin, since it does not specifically recognize the sugars lactose and sialic acid. The lectinic T-cell factor reduces the release by APCs of IFNα - a key cytokine known to inhibit the proliferation of activated T-lymphocytes.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Les kinoïdes

Depuis maintenant plus d’un siècle, les vaccins font partie de l’arsenal thérapeutique servant à combattre et maîtriser un grand nombre d’infections. À la faveur des progrès biotechnologiques et d’une meilleure connaissance de la physiopathologie associée à certaines affections chroniques, l’innocuité, l’immunogénicité et l’efficacité des préparations vaccinales ont été améliorées (épitopes antigéniques mieux ciblés, adjuvants non toxiques…). Malgré ces efforts, l’approche vaccinale thérapeutique conventionnelle reste inefficace dans certains cas comme le Sida ou les cancers. Pour expliquer ces échecs thérapeutiques, nous avons postulé que l’échappement immunitaire des cellules malades, infectées par un virus ou tumorales, pouvait être lié à des dysfonctionnements cytokiniques pouvant contribuer à une paralysie immunitaire

Kinoids: A family of immunogens for active anticytokine immunotherapy applied to autoimmune diseases and cancer

The complex homeostasis of tissues is coordinated by the cytokine network and imbalances in this network may result in chronic immune disorders. Key specific cytokines, such as TNF-α, IFN-α, IL-4 or VEGF have been demonstrated to be overproduced or abnormally released in the microenvironment of pathologic tissues. These findings have opened up the way to passive immunotherapy with anticytokine monoclonal antibodies. Even though passive immunotherapy has proved to be efficient, it is hampered by specific limitations. The discovery of a family of immunogens, the kinoids, consisting of inactivated cytokine derivatives, has led some to propose them for active immunotherapy as an alternative to passive immunotherapy. This review focuses on kinoids - on their validation in experimental mouse models and ongoing clinical trials. The advantages offered by this active immune therapy in terms of efficacy, safety and patient compliance will be stressed. © 2010 Future Medicine Ltd.SCOPUS: re.jinfo:eu-repo/semantics/publishe

Active versus passive anti-cytokine antibody therapy against cytokine-associated chronic diseases

Current therapeutic vaccine trials in major chronic diseases including AIDS, cancer, allergy and autoimmunity, target antigenic pathogens but not the pathogenic stromal cytokines which can be major sources of histopathologic processes. Considering that the limited efficacy of these vaccines has been ascribed to local pathogen-induced cytokine dysfunction, we propose to antagonize pathogenic cytokine(s) by high affinity neutralizing auto-Abs triggered by specific anti-cytokine vaccines. As anticipated by theoretical considerations, animal experiments and initial clinical trials showed that anti-cytokine immunization was safe, well tolerated and triggered transient high titers Abs neutralizing pathogenic cytokines but, in contrast to conventional vaccines, no relevant cellular response was observed. Advantages of active versus passive anti-cytokine Ab therapy, particularly for long-term treatments, as those required in AIDS, cancer, allergy and autoimmunity include greater ease of maintaining high Ab titers, lack of anti-antibody responses and low cost. © 2003 Elsevier Science Ltd. All rights reserved.SCOPUS: re.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

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

Early and long-lasting protection from arthritis in tumour necrosis factor α (TNFα) transgenic mice vaccinated against TNFα

Objective: To evaluate the effect in mice with arthritis of active anti-tumour necrosis factor (TNF)α immunotherapy based on a keyhole limpet haemocyanin-human TNFα heterocomplex (hTNFα kinoid or TNFK) adjuvanted in incomplete Freund adjuvant. Immunotherapy was evaluated also with methotrexate. Methods: Human TNFα-transgenic mice received TNFK with or without methotrexate. Follow-up ranged from 6 weeks (short term) to 17 weeks (long term). Arthritis was evaluated clinically and histologically. Monitoring included titration of anti-hTNFα antibodies by ELISA and neutralisation assay. Results: Vaccination with TNFK was associated with rapid-onset, long-lasting protection. Long-term results showed significantly milder arthritis in vaccinated animals than in control animals at the peak of the disease. Vaccination was followed by resolution of the clinical evidence of arthritis, contrasting with severe progressive arthritis in the control group. Histological improvements with decreased inflammation and destruction were noted in all immunised groups, even after the shortest follow-up (6 weeks). High titres of neutralising anti-hTNFα antibodies were detected as early as the fifth week post immunisation and persisted over time. Methotrexate given concomitantly with the vaccine did not influence either the effect on arthritis or the anti-hTNFα antibody titres. Conclusion: Anti-cytokine induction of autoimmune protection against chronic hTNFα overproduction is an efficient alternative to TNFα blockade in experimental arthritis and can be achieved using a TNFK vaccine.SCOPUS: ar.jinfo:eu-repo/semantics/publishe