Document Detail


Incorporation of CD40 ligand into SHIV virus-like particles (VLP) enhances SHIV-VLP-induced dendritic cell activation and boosts immune responses against HIV.
MedLine Citation:
PMID:  20471443     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Engagement of CD40 with CD40L induces dendritic cell (DC) maturation and activation, thereby promoting immune responses. The objective of this study was to investigate whether immunization with chimeric CD40L/SHIV virus-like particles (CD40L/SHIV-VLP) could enhance immune responses to SIV Gag and HIV Env proteins by directly activating DCs. We found that CD83, CD40, and CD86 were significantly up-regulated and significantly increased cytokines production were observed after hCD40L/SHIV-VLP treatment in human CD14(+) monocyte-derived DCs as compared to SHIV-VLP treatment. Mice immunized with mCD40L/SHIV-VLP showed more than a two-fold increase in HIV Env-specific IgG antibody production, an increase in SIV Gag and HIV Env-specific IFN-gamma and IL-4 producing cells, and an increase in HIV Env-specific cytotoxic activity compared to that in SHIV-VLP immunized mice. Furthermore, multifunctional CD4(+) Th1 cells, which simultaneously produce IFN-gamma, IL-2 and TNF-alpha triple cytokines, and CD8(+) T-cells, which produce IFN-gamma were elevated in the mCD40L/SHIV-VLP immunized group. These data demonstrate that chimeric CD40L/SHIV-VLP potently induce DC activation and enhance the magnitude of both humoral and cellular immune responses to the SIV Gag and HIV Env proteins in the mouse model. Therefore, incorporation of CD40L into VLP may represent a novel strategy to develop effective HIV vaccines.
Authors:
Rongxin Zhang; Sheng Zhang; Min Li; Changyi Chen; Qizhi Yao
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural     Date:  2010-05-14
Journal Detail:
Title:  Vaccine     Volume:  28     ISSN:  1873-2518     ISO Abbreviation:  Vaccine     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-07-19     Completed Date:  2010-09-22     Revised Date:  2011-09-26    
Medline Journal Info:
Nlm Unique ID:  8406899     Medline TA:  Vaccine     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  5114-27     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier Ltd. All rights reserved.
Affiliation:
Molecular Surgeon Research Center, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, United States.
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MeSH Terms
Descriptor/Qualifier:
AIDS Vaccines / immunology*
Animals
CD40 Ligand / immunology*
Cells, Cultured
Dendritic Cells / immunology*
HIV / immunology
HIV Antibodies / blood
HIV Infections / immunology,  prevention & control*
Humans
Immunoglobulin G / blood
Interferon-gamma / immunology
Interleukin-4 / immunology
Mice
Mice, Inbred C57BL
Simian immunodeficiency virus / immunology
T-Lymphocytes / immunology
Tumor Necrosis Factor-alpha / immunology
Grant Support
ID/Acronym/Agency:
AI053831/AI/NIAID NIH HHS; AT003094/AT/NCCAM NIH HHS; DE015543/DE/NIDCR NIH HHS; R01 DE015543-04/DE/NIDCR NIH HHS; R21 AT003094-02/AT/NCCAM NIH HHS
Chemical
Reg. No./Substance:
0/AIDS Vaccines; 0/HIV Antibodies; 0/Immunoglobulin G; 0/Tumor Necrosis Factor-alpha; 147205-72-9/CD40 Ligand; 207137-56-2/Interleukin-4; 82115-62-6/Interferon-gamma
Comments/Corrections

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


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