Institute of Tropical Medicine Antwerp
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mRNA-based dendritic cell vaccination induces potent antiviral T-cell responses in HIV-1-infected patients

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Show simple item record Van Gulck, E. Vlieghe, E. Vekemans, M. Van Tendeloo, V. F. Van de Velde, A. Smits, E. Anguille, S. Cools, N. Goossens, H. Mertens, L. De Haes, W. Wong, J. Florence, E. Vanham, G. Berneman, Z. N. 2012-02-29T11:03:34Z 2012-02-29T11:03:34Z 2012
dc.identifier.issn 0269-9370
dc.identifier.other ITG-B1B
dc.identifier.other ITG-C2A
dc.identifier.other ITG-C3A
dc.identifier.other ITG-C10B
dc.identifier.other ITG-B11B
dc.identifier.other ITG-C13A
dc.identifier.other ITG-C14A
dc.identifier.other MULTI
dc.identifier.other DBM
dc.identifier.other U-VIROL
dc.identifier.other DCS
dc.identifier.other U-TROPIC
dc.identifier.other U-TRAVM
dc.identifier.other U-STDCLI
dc.identifier.other JIF
dc.identifier.other DOI
dc.identifier.other UPD43
dc.description.abstract BACKGROUND: In an effort to raise protective antiviral immunity, dendritic cell (DC) immunotherapy was evaluated in 6 adults infected with human immunodeficiency virus (HIV)-1 and stable under antiretroviral therapy (HAART). DESIGN & METHODS:: Autologous monocyte-derived DC electroporated with mRNA encoding Gag and a chimeric Tat-Rev-Nef protein were administered, while patients remained on HAART. Feasibility, safety, immunogenicity and antiviral responses were investigated. RESULTS: DC vaccine preparation and administration were successful in all patients and only mild adverse events were seen. There was a significant increase post-DC as compared to pre-DC vaccination in magnitude and breadth of HIV-1-specific interferon (IFN)-gamma response, in particular to Gag, and in T-cell proliferation. Breadth of IFN-gamma response and T-cell proliferation were both correlated with CD4+ and CD8+ polyfunctional T-cell responses. Importantly, DC 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-gamma response. CONCLUSIONS: Therapeutic immunization with DC 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 DC vaccination in the treatment of HIV-1. The incomplete nature of the response in some patients helped to identify potential targets for future improvement, i.e. increasing antigenic spectrum and enhancing T-cell response. en
dc.language English en
dc.subject Viral diseases en
dc.subject HIV-1 en
dc.subject AIDS en
dc.subject HAART en
dc.subject Antiretrovirals en
dc.subject Immunotherapy en
dc.subject Vaccination en
dc.subject Immunity en
dc.subject mRNA en
dc.subject Dendritic cells en
dc.subject T-cells en
dc.subject Gag en
dc.subject Tat en
dc.subject Evaluation en
dc.subject Feasibility en
dc.subject Safety en
dc.subject Immunogenicity en
dc.subject IFN-g en
dc.subject CD4-positive-T-lymphocytes en
dc.subject CD8-positive-T-lymphocytes en
dc.title mRNA-based dendritic cell vaccination induces potent antiviral T-cell responses in HIV-1-infected patients en
dc.type Article en
dc.citation.issue 4 en
dc.citation.jtitle AIDS en
dc.citation.volume 26 en
dc.citation.pages F1-F12 en
dc.citation.jabbreviation AIDS en

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