Abstract
The development of an effective vaccine against HIV infection remains a global priority. Dendritic cell (DC)-based HIV immunotherapeutic vaccine is a promising approach which aims at optimizing the HIV-specific immune response using primed DCs to promote and enhance both the cellular and humoral arms of immunity. Since the Ebola virus envelope glycoprotein (EboGP) has strong DC-targeting ability, we investigated whether EboGP is able to direct HIV particles towards DCs efficiently and promote potent HIV-specific immune responses. Our results indicate that the incorporation of EboGP into non-replicating virus-like particles (VLPs) enhances their ability to target human monocyte-derived dendritic cells (MDDCs) and monocyte-derived macrophages (MDMs). Also, a mucin-like domain deleted EboGP (EboGPΔM) can further enhanced the MDDCs and MDMs-targeting ability. Furthermore, we investigated the effect of EboGP on HIV immunogenicity in mice, and the results revealed a significantly stronger HIV-specific humoral immune response when immunized with EboGP-pseudotyped HIV VLPs compared with those immunized with HIV VLPs. Splenocytes harvested from mice immunized with EboGP-pseudotyped HIV VLPs secreted increased levels of macrophage inflammatory proteins-1α (MIP-1α) and IL-4 upon stimulation with HIV Env and/or Gag peptides compared with those harvested from mice immunized with HIV VLPs. Collectively, this study provides evidence for the first time that the incorporation of EboGP in HIV VLPs can facilitate DC and macrophage targeting and induce more potent immune responses against HIV.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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AIDS Vaccines / administration & dosage
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AIDS Vaccines / genetics
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AIDS Vaccines / immunology*
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Animals
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Chemokine CCL3 / genetics
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Chemokine CCL3 / immunology
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Dendritic Cells / drug effects*
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Dendritic Cells / immunology
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Dendritic Cells / virology
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Ebolavirus / chemistry
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Female
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Gene Expression
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HEK293 Cells
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HIV Antibodies / biosynthesis*
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HIV Infections / immunology
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HIV Infections / prevention & control*
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HIV Infections / virology
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HIV-1 / drug effects
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HIV-1 / growth & development
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HIV-1 / immunology
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Humans
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Immunity, Cellular / drug effects
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Immunity, Humoral / drug effects
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Immunization
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Immunogenicity, Vaccine
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Interleukin-4 / genetics
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Interleukin-4 / immunology
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Lymphocytes / cytology
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Lymphocytes / drug effects
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Lymphocytes / immunology
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Macrophages / drug effects*
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Macrophages / immunology
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Macrophages / virology
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Mice
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Mice, Inbred C57BL
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Molecular Targeted Therapy
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Primary Cell Culture
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Spleen / cytology
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Spleen / drug effects
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Spleen / immunology
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Vaccines, Virus-Like Particle / administration & dosage
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Vaccines, Virus-Like Particle / genetics
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Vaccines, Virus-Like Particle / immunology*
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Viral Envelope Proteins / genetics*
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Viral Envelope Proteins / immunology
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env Gene Products, Human Immunodeficiency Virus / genetics
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env Gene Products, Human Immunodeficiency Virus / immunology
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gag Gene Products, Human Immunodeficiency Virus / genetics
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gag Gene Products, Human Immunodeficiency Virus / immunology
Substances
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AIDS Vaccines
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Ccl3 protein, mouse
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Chemokine CCL3
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HIV Antibodies
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Vaccines, Virus-Like Particle
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Viral Envelope Proteins
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env Gene Products, Human Immunodeficiency Virus
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envelope glycoprotein, Ebola virus
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gag Gene Products, Human Immunodeficiency Virus
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Interleukin-4