Document Detail


Effects of MIP-1 alpha, MIP-3 alpha, and MIP-3 beta on the induction of HIV Gag-specific immune response with DNA vaccines.
MedLine Citation:
PMID:  17356539     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Ruijiang Song; Shuqin Liu; Kam W Leong
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2007-03-13
Journal Detail:
Title:  Molecular therapy : the journal of the American Society of Gene Therapy     Volume:  15     ISSN:  1525-0016     ISO Abbreviation:  Mol. Ther.     Publication Date:  2007 May 
Date Detail:
Created Date:  2007-04-20     Completed Date:  2007-09-25     Revised Date:  2011-09-26    
Medline Journal Info:
Nlm Unique ID:  100890581     Medline TA:  Mol Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1007-15     Citation Subset:  IM    
Affiliation:
Department of Pharmacology and Molecular Biology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line
Chemokine CCL4
Chemotaxis / immunology
Dendritic Cells / immunology
Enzyme-Linked Immunosorbent Assay
Female
Flow Cytometry
Gene Products, gag / genetics,  immunology*
HIV / genetics,  immunology*
Humans
Macrophage Inflammatory Proteins / genetics,  immunology*,  metabolism
Mice
Mice, Inbred BALB C
Microscopy, Fluorescence
Plasmids / administration & dosage,  genetics
Protein Isoforms / genetics,  immunology,  metabolism
T-Lymphocytes, Cytotoxic / immunology
Vaccination / methods
Vaccines, DNA / administration & dosage,  genetics,  immunology*
Grant Support
ID/Acronym/Agency:
EB002849/EB/NIBIB NIH HHS; R01 EB002849-01/EB/NIBIB NIH HHS
Chemical
Reg. No./Substance:
0/Chemokine CCL4; 0/Gene Products, gag; 0/Macrophage Inflammatory Proteins; 0/Protein Isoforms; 0/Vaccines, DNA
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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