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

• Published in: Gene therapy Vol. 17; no. 11; pp. 1372 - 1383
• Main Authors: Kutscher, S, Allgayer, S, Dembek, C J, Bogner, J R, Protzer, U, Goebel, F D, Erfle, V, Cosma, A
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.11.2010; Nature Publishing Group
• Subjects: 631/326/596/2561; 692/699/249/1570/1901; 692/700/565/251/1567; AIDS Vaccines - immunology; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Antiretroviral Therapy, Highly Active; Applied cell therapy and gene therapy; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Biotechnology; CD154 antigen; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD40L protein; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Cell Biology; Cell growth; Cell Proliferation; Clinical trials; Esters; Flow cytometry; Fundamental and applied biological sciences. Psychology; gamma -Interferon; Gene Expression; Gene Therapy; Genetic Vectors - genetics; Health. Pharmaceutical industry; Highly active antiretroviral therapy; HIV; HIV Infections - immunology; HIV-1 - genetics; HIV-1 - immunology; Human Genetics; Human immunodeficiency virus; Human immunodeficiency virus 1; Humans; Immune response; Immune system; Immunization; Immunoassay; Immunogenicity; Industrial applications and implications. Economical aspects; Infection; Interferon-gamma - metabolism; Interleukin 2; Lymphocyte Activation - genetics; Lymphocyte Activation - immunology; Lymphocytes; Lymphocytes T; Medical sciences; Nanotechnology; nef Gene Products, Human Immunodeficiency Virus - genetics; nef Gene Products, Human Immunodeficiency Virus - immunology; Nef protein; original-article; Patient outcomes; Physiological aspects; Properties; T cells; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Vaccination; Vaccines; Vaccines, DNA - immunology; Vaccinia virus; Vaccinia virus - genetics; Viruses; γ-Interferon; Germany; HIV-1; MVA; proliferation; therapeutic vaccination; T-cell response; Cell proliferation; Vaccination; Retroviridae; Lentivirus; Virus; T-Lymphocyte; Human immunodeficiency virus; Gene therapy
• ISSN: 0969-7128; 1476-5462; 1476-5462
• DOI: 10.1038/gt.2010.90

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.