Abstract
Despite significant therapeutic advances for HIV-1 infected individuals, a preventative HIV-1 vaccine remains elusive. Studies focusing on early transmission events, including the observation that there is a profound loss of gastrointestinal (GI) CD4(+) T cells during acute HIV-1 infection, highlight the importance of inducing HIV-specific immunity within the gut. Here we report on the generation of cellular and humoral immune responses in the intestines by a mucosally administered, dendritic cell (DC) targeted vaccine. Our results show that nasally delivered α-CD205-p24 vaccine in combination with polyICLC, induced polyfunctional immune responses within naso-pulmonary lymphoid sites that disseminated widely to systemic and mucosal (GI tract and the vaginal epithelium) sites. Qualitatively, while α-CD205-p24 prime-boost immunization generated CD4(+) T-cell responses, heterologous prime-boost immunization with α-CD205-p24 and NYVAC gag-p24 generated high levels of HIV-specific CD4(+) and CD8(+) T cells within the GI tract. Finally, DC-targeting enhanced the amplitude and longevity of vaccine-induced immune responses in the GI tract. This is the first report of a nasally delivered, DC-targeted vaccine to generate HIV-specific immune responses in the GI tract and will potentially inform the design of preventative approaches against HIV-1 and other mucosal infections.
MeSH terms
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AIDS Vaccines / administration & dosage
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AIDS Vaccines / biosynthesis
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AIDS Vaccines / immunology*
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Administration, Intranasal
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Animals
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Antigens, CD / genetics
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Antigens, CD / immunology
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Antigens, Viral / genetics
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Antigens, Viral / immunology
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CD4-Positive T-Lymphocytes / cytology
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CD4-Positive T-Lymphocytes / drug effects*
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CD4-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / cytology
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CD8-Positive T-Lymphocytes / drug effects*
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CD8-Positive T-Lymphocytes / immunology
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Carboxymethylcellulose Sodium / analogs & derivatives
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Carboxymethylcellulose Sodium / pharmacology
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Dendritic Cells / cytology
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Dendritic Cells / drug effects*
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Dendritic Cells / immunology
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Female
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Gastrointestinal Tract / cytology
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Gastrointestinal Tract / drug effects*
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Gastrointestinal Tract / immunology
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HIV Core Protein p24 / genetics
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HIV Core Protein p24 / immunology
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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 / genetics
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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, Secondary
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Interferon Inducers / pharmacology
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Lectins, C-Type / genetics
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Lectins, C-Type / immunology
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Minor Histocompatibility Antigens / genetics
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Minor Histocompatibility Antigens / immunology
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Poly I-C / pharmacology
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Polylysine / analogs & derivatives
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Polylysine / pharmacology
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Receptors, Cell Surface / genetics
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Receptors, Cell Surface / immunology
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Vaccination / methods
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Viral Vaccines / administration & dosage
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Viral Vaccines / 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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Antigens, CD
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Antigens, Viral
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DEC-205 receptor
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HIV Core Protein p24
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Interferon Inducers
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Lectins, C-Type
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Minor Histocompatibility Antigens
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NYVAC vaccine
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Receptors, Cell Surface
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Viral Vaccines
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gag Gene Products, Human Immunodeficiency Virus
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Polylysine
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poly ICLC
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Carboxymethylcellulose Sodium
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Poly I-C