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Kutscher, S. ; Allgayer, S. ; Dembek, C.J. ; Bogner, J.R.* ; Protzer, U. ; Goebel, F.D.* ; Erfle, V.* ; Cosma, A.

MVA-nef induces HIV-1-specific polyfunctional and proliferative T-cell responses revealed by the combination of short- and long-term immune assays.

Gene Ther. 17, 1372-1383 (2010)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Several vaccination trials are evaluating the modified vaccinia virus Ankara (MVA) as a delivery vector in various clinical settings. In this paper, we present the reevaluation of a therapeutic vaccination trial in human immunodeficiency virus (HIV)-1-infected individuals treated with highly active antiretroviral therapy using MVA-expressing HIV-1 nef. Immunogenicity of MVA-nef was assessed using multicolor flow cytometry. Vaccine-induced polyfunctionality and proliferative capacity, which are associated with nonprogressive HIV-1 infection, were detectable by combining two immune assays. By means of short-term polychromatic intracellular cytokine staining, we observed a significant increase in polyfunctional Nef-specific CD4 T cells expressing interferon-γ, interleukin (IL)-2 and CD154 after vaccination, whereas changes in the quality of CD8 T-cell response could not be observed. Only the additional use of a long-term polychromatic Carboxyfluorescein succinimidyl ester (CFSE)-based proliferation assay revealed vaccine-induced Nef-specific CD8, as well as CD4 T cells with proliferative capacity. The correlation between vaccine-induced IL-2 production by CD4 T cells and the increase in proliferating Nef-specific CD8 T cells suggests a causal link between these two functions. These results highlight the importance of combining sophisticated immunomonitoring tools to unravel concealed effects of immunological interventions and support the use of the poxvirus-derived MVA vector to stimulate highly functional HIV-1-specific T-cell responses. However, the clinical benefit of these functional T cells remains to be determined.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords HIV-1; Therapeutic vaccination; MVA; T-cell response; Proliferation
ISSN (print) / ISBN 0969-7128
e-ISSN 1476-5462
Journal Gene Therapy
Quellenangaben Volume: 17, Issue: 11, Pages: 1372-1383 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Virology (VIRO)
CCG Immune Monitoring (Platform) (IMI-KIM)