Abstract
Immunostimulatory DNA sequences (ISS) are a potent Th1 adjuvant. We hypothesized that conjugation of ISS to protein antigens would strongly enhance their immunogenicity because both antigen and adjuvant (ISS) would be delivered to the same locale/antigen-presenting cell. To test this hypothesis, we conjugated a 22-mer immunostimulatory oligodeoxynucleotide (ISS-ODN) to two test antigens of differing intrinsic immunogenicity, namely Escherichia coli beta-galactosidase and the HIV-1 envelope glycoprotein gp120. We show that the antigen-ISS conjugates rapidly induce Th1 cells secreting high levels of IFN-gamma, strong CTL activity, and high titer IgG2a and HIV-neutralizing antibodies, exceeding gene and protein vaccination alone or immunization with mixtures of antigen and ISS-ODN. The data suggest that this procedure generates a novel and unique vaccine that rapidly triggers strong humoral and cell-mediated immunity.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antibodies, Bacterial / blood*
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Antibodies, Bacterial / immunology
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Antibody Formation / immunology
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CHO Cells
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Cricetinae
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Electrophoresis, Polyacrylamide Gel / methods
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Escherichia coli / enzymology
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Female
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HIV Antibodies / blood*
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HIV Antibodies / immunology
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HIV Envelope Protein gp120 / genetics
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HIV Envelope Protein gp120 / immunology*
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Immunity, Cellular / immunology
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Immunoglobulin G / blood
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Immunoglobulin G / immunology
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Interferon-gamma / metabolism*
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Mice
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Mice, Inbred BALB C
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Oligodeoxyribonucleotides / immunology*
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Plasmids / immunology
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Sodium Dodecyl Sulfate
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T-Lymphocytes, Cytotoxic / immunology*
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Th1 Cells / immunology*
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Th1 Cells / metabolism
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Thionucleotides / immunology*
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Time Factors
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beta-Galactosidase / genetics
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beta-Galactosidase / immunology*
Substances
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Antibodies, Bacterial
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HIV Antibodies
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HIV Envelope Protein gp120
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Immunoglobulin G
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Oligodeoxyribonucleotides
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Thionucleotides
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Sodium Dodecyl Sulfate
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Interferon-gamma
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beta-Galactosidase