mRNA-based dendritic cell vaccination induces potent antiviral T-cell responses in HIV-1-infected patients
| Autor: | Marc Vekemans, Evelien Smits, Ann Van de Velde, Liesbet Mertens, Johnsson Wong, Guido Vanham, Ellen Van Gulck, Viggo Van Tendeloo, Erika Vlieghe, Zwi N. Berneman, Sébastien Anguille, Eric Florence, H. Goossens, Winni De Haes, Nathalie Cools |
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| Rok vydání: | 2011 |
| Předmět: |
CD4-Positive T-Lymphocytes
Male HAART CD4-positive-T-lymphocytes medicine.medical_treatment T-Lymphocytes Human Immunodeficiency Virus Proteins CD8-positive-T-lymphocytes HIV Infections CD8-Positive T-Lymphocytes Lymphocyte Activation gag Gene Products Human Immunodeficiency Virus Interferon Antiretroviral Therapy Highly Active Immunology and Allergy Evaluation Gag AIDS Vaccines Vaccination virus diseases Antiretrovirals Feasibility Middle Aged Immunogenicity AIDS Infectious Diseases medicine.anatomical_structure Electroporation RNA Viral tat Gene Products Human Immunodeficiency Virus Immunotherapy Safety medicine.drug Adult T cell mRNA Recombinant Fusion Proteins Immunology Viral diseases Biology Antiviral Agents Virus IFN-g Interferon-gamma Immune system Antigen medicine Humans RNA Messenger nef Gene Products Human Immunodeficiency Virus T-cells Immunity rev Gene Products Human Immunodeficiency Virus Dendritic cell Dendritic Cells Virology HIV-1 Feasibility Studies Human medicine Tat CD8 |
| Zdroj: | AIDS |
| ISSN: | 1473-5571 0269-9370 |
| Popis: | Background: In an effort to raise protective antiviral immunity, dendritic cell immunotherapy was evaluated in six adults infected with human immunodeficiency virus (HIV)-1 and stable under highly active antiretroviral therapy (HAART). Design and Methods: Autologous monocyte-derived dendritic cells electroporated with mRNA encoding Gag and a chimeric Tat-Rev-Nef protein were administered, whereas patients remained on HAART. Feasibility, safety, immunogenicity and antiviral responses were investigated. Results: Dendritic cell vaccine preparation and administration were successful in all patients and only mild adverse events were seen. There was a significant increase post-dendritic cell as compared to pre-dendritic cell vaccination in magnitude and breadth of HIV-1-specific interferon (IFN)-γ response, in particular to Gag, and in T-cell proliferation. Breadth of IFN-γ response and T-cell proliferation were both correlated with CD4 + and CD8 + polyfunctional T-cell responses. Importantly, dendritic cell vaccination induced or increased the capacity of autologous CD8 + T cells to inhibit superinfection of CD4 + T cells with the vaccine-related IIIB virus and some but not all other HIV-1 strains tested. This HIV-1-inhibitory activity, indicative of improved antiviral response, was correlated with magnitude and breadth of Gag-specific IFN-γ response. Conclusions: Therapeutic immunization with dendritic cells was safe and successful in raising antiviral cellular immune responses, including effector CD8 + T cells with virus inhibitory activity. The stimulation of those potent immunological and antiviral effects, which have been associated with control of HIV-1, underscores the potential of dendritic cell vaccination in the treatment of HIV-1. The incomplete nature of the response in some patients helped to identify potential targets for future improvement, that is increasing antigenic spectrum and enhancing T-cell response. © 2012 Wolters Kluwer Health |
| Databáze: | OpenAIRE |
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