Functional T-cell responses generated by dendritic cells expressing the early HIV-1 proteins Tat, Rev and Nef

Sabine D Allard; Katrien Pletinckx; Karine Breckpot; Carlo Heirman; Aude Bonehill; Annelies Michiels; Carel A van Baalen; Rob A Gruters; Albert D M E Osterhaus; Patrick Lacor; Kris Thielemans; Joeri L Aerts

doi:10.1016/j.vaccine.2008.04.077

Functional T-cell responses generated by dendritic cells expressing the early HIV-1 proteins Tat, Rev and Nef

Vaccine. 2008 Jul 4;26(29-30):3735-41. doi: 10.1016/j.vaccine.2008.04.077. Epub 2008 May 20.

Authors

Sabine D Allard¹, Katrien Pletinckx, Karine Breckpot, Carlo Heirman, Aude Bonehill, Annelies Michiels, Carel A van Baalen, Rob A Gruters, Albert D M E Osterhaus, Patrick Lacor, Kris Thielemans, Joeri L Aerts

Affiliation

¹ The Laboratory of Molecular and Cellular Therapy, Department of Physiology and Immunology, Medical School of the Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium. sabine.allard@uzbrussel.be

PMID: 18539368
DOI: 10.1016/j.vaccine.2008.04.077

Abstract

The limitations of highly active anti-retroviral therapy (HAART) have necessitated the development of alternative therapeutic strategies. One of the approaches that has gained prominence in recent years is therapeutic vaccination. We decided to assess the capacity of mature dendritic cells, derived from blood monocytes of HIV-1 infected patients, to generate functional T-cell responses. For this purpose, we constructed a chimeric mRNA encoding the proteins Tat, Rev and Nef. The TaReNef encoding information was linked to the HLA class II-targeting sequence of DC-LAMP. Broadly directed HIV-specific CD4(+) and CD8(+) cytotoxic T cells exhibiting a poly-functional cytokine secretion pattern were generated by co-culturing with autologous chimeric mRNA electroporated dendritic cells. Thus, administration of ex vivo generated dendritic cells expressing the early proteins Tat, Rev and Nef might offer a promising approach for therapeutic vaccination in HIV-1 infection.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
CD4-Positive T-Lymphocytes / immunology*
CD8-Positive T-Lymphocytes / immunology*
Coculture Techniques
Cytokines / metabolism
Dendritic Cells / immunology*
Electroporation
HIV Infections / immunology
Humans
Lysosomal Membrane Proteins / genetics
Lysosomal Membrane Proteins / immunology
Male
Middle Aged
Molecular Sequence Data
Recombinant Fusion Proteins / genetics
Recombinant Fusion Proteins / immunology
Sequence Analysis, DNA
nef Gene Products, Human Immunodeficiency Virus / biosynthesis
nef Gene Products, Human Immunodeficiency Virus / immunology*
rev Gene Products, Human Immunodeficiency Virus / biosynthesis
rev Gene Products, Human Immunodeficiency Virus / immunology*
tat Gene Products, Human Immunodeficiency Virus / biosynthesis
tat Gene Products, Human Immunodeficiency Virus / immunology*

Substances

Cytokines
Lysosomal Membrane Proteins
Recombinant Fusion Proteins
nef Gene Products, Human Immunodeficiency Virus
nef protein, Human immunodeficiency virus 1
rev Gene Products, Human Immunodeficiency Virus
rev protein, Human Immunodeficiency Virus-1
tat Gene Products, Human Immunodeficiency Virus

Associated data

GENBANK/DQ668404
GENBANK/DQ668405