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Effects of MIP-1 alpha, MIP-3 alpha, and MIP-3 beta on the induction of HIV Gag-specific immune response with DNA vaccines.
- Source :
-
Molecular therapy : the journal of the American Society of Gene Therapy [Mol Ther] 2007 May; Vol. 15 (5), pp. 1007-15. Date of Electronic Publication: 2007 Mar 13. - Publication Year :
- 2007
-
Abstract
- Transfection of DNA vaccines with chemokines may recruit dendritic cells (DCs) locally to capture the antigenic genes and their gene products to generate enhanced CD8(+) cytotoxic T lymphocytes (CTLs). In this study, we investigated the effects of macrophage inflammatory protein (MIP)-1 alpha, MIP-3 alpha, and MIP-3beta on human immunodeficiency virus (HIV) Gag DNA vaccination. The chemokine plasmids markedly enhanced the local infiltration of inflammatory cells and increased the presence of CD11c(+) B7.2(+)-activated DCs. MIP-1 alpha and MIP-3 alpha were potent adjuvants in augmenting CTLs and afforded strong protection to immunized animals against challenge with vaccinia virus expressing Gag (vv-Gag). However, decreased humoral response was observed. MIP-3beta plasmid did not dramatically alter immunity. The chemokine inoculation time with respect to DNA vaccine priming was also investigated. The injection of pMIP-3 alpha three days before Gag plasmid (pGag) vaccination markedly increased specific CTLs compared with simultaneous injection and led to higher protection against vv-Gag. Immunity was also shifted toward a T-helper type-1 (Th1) response. In contrast, inoculation with pMIP-3 alpha three days after pGag vaccination shifted immunity toward a Th2 response. Our data suggest that administration of a chemokine with DNA vaccines offers a valuable strategy to modulate the efficacy and polarization of specific immunity and that chemokine-antigen timing is critical in determining overall biological effects.
- Subjects :
- Animals
Cell Line
Chemokine CCL4
Chemotaxis immunology
Dendritic Cells immunology
Enzyme-Linked Immunosorbent Assay
Female
Flow Cytometry
Gene Products, gag genetics
HIV genetics
Humans
Macrophage Inflammatory Proteins genetics
Macrophage Inflammatory Proteins metabolism
Mice
Mice, Inbred BALB C
Microscopy, Fluorescence
Plasmids administration & dosage
Plasmids genetics
Protein Isoforms genetics
Protein Isoforms immunology
Protein Isoforms metabolism
T-Lymphocytes, Cytotoxic immunology
Vaccination methods
Vaccines, DNA administration & dosage
Vaccines, DNA genetics
Gene Products, gag immunology
HIV immunology
Macrophage Inflammatory Proteins immunology
Vaccines, DNA immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1525-0016
- Volume :
- 15
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Molecular therapy : the journal of the American Society of Gene Therapy
- Publication Type :
- Academic Journal
- Accession number :
- 17356539
- Full Text :
- https://doi.org/10.1038/mt.sj.6300129