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MVA-nef induces HIV-1-specific polyfunctional and proliferative T-cell responses revealed by the combination of short- and long-term immune assays.
- Source :
- Gene Therapy; Nov2010, Vol. 17 Issue 11, p1372-1383, 12p, 1 Diagram, 4 Graphs
- Publication Year :
- 2010
-
Abstract
- 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- HIV infections
VACCINATION
HIGHLY active antiretroviral therapy
CYTOKINES
T cells
Subjects
Details
- Language :
- English
- ISSN :
- 09697128
- Volume :
- 17
- Issue :
- 11
- Database :
- Complementary Index
- Journal :
- Gene Therapy
- Publication Type :
- Academic Journal
- Accession number :
- 55113672
- Full Text :
- https://doi.org/10.1038/gt.2010.90