Publication
Title
mRNA-based dendritic cell vaccination induces potent antiviral T-cell responses in HIV-1-infected patients
Author
Abstract
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.
Language
English
Source (journal)
AIDS. - London
Publication
London : 2012
ISSN
0269-9370
Volume/pages
26:4(2012), p. F1-F12
ISI
000300411500001
Full text (Publisher's DOI)
UAntwerpen
Faculty/Department
Research group
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 17.02.2012
Last edited 07.07.2017
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