Abstract
We have constructed stable virus-like particles displaying the HIV-1 Gag(p17) protein as an N-terminal fusion with an engineered protein domain from the Geobacillus stearothermophilus pyruvate dehydrogenase subunit E2. Mice immunized with the Gag(p17)-E2 60-mer scaffold particles mounted a strong and sustained antibody response. Antibodies directed to Gag(p17) were boosted significantly with additional immunizations, while anti-E2 responses reached a plateau. The isotype of the induced antibodies was biased towards IgG1, and the E2-primed CD4+ T cells did not secrete IFNγ. Using transgenic mouse model systems, we demonstrated that CD8+ T cells primed with E2 particles were able to exert lytic activity and produce IFNγ. These results show that the E2 scaffold represents a powerful vaccine delivery system for whole antigenic proteins or polyepitope engineered proteins, evoking antibody production and antigen specific CTL activity even in the absence of IFNγ-producing CD4+ T cells.
Copyright © 2010 Elsevier Inc. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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AIDS Vaccines / immunology*
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Acyltransferases / genetics
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Acyltransferases / immunology
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Acyltransferases / metabolism
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Animals
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B-Lymphocytes / immunology
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Bacterial Proteins / genetics
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Bacterial Proteins / metabolism
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CD4-Positive T-Lymphocytes / metabolism
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Female
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Genetic Vectors*
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Geobacillus stearothermophilus / enzymology
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Geobacillus stearothermophilus / genetics
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Geobacillus stearothermophilus / immunology
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Geobacillus stearothermophilus / metabolism*
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HIV Antibodies / blood*
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HIV-1 / genetics
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HIV-1 / immunology
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HIV-1 / metabolism
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Humans
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Immunization
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Interferon-gamma / biosynthesis
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Lymphocyte Activation / 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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Peptide Fragments / genetics
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Peptide Fragments / immunology*
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Peptide Fragments / metabolism
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / immunology
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Recombinant Fusion Proteins / metabolism
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T-Lymphocytes / immunology
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Virion / 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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env Gene Products, Human Immunodeficiency Virus / metabolism
Substances
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AIDS Vaccines
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Bacterial Proteins
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HIV Antibodies
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Peptide Fragments
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Recombinant Fusion Proteins
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env Gene Products, Human Immunodeficiency Virus
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p17 gag peptide, human immunodeficiency virus
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Interferon-gamma
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Acyltransferases