Conjugation of protein to immunostimulatory DNA results in a rapid, long-lasting and potent induction of cell-mediated and humoral immunity.
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.
Department of Medicine, The Sam and Rose Stein Institute for Research of Aging, University of California, San Diego, La Jolla 92093-0663, USA. htighe@ucsd.edu
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H
Tighe
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Takabayashi
D
D
Schwartz
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R
Marsden
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L
Beck
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J
Corbeil
D D
DD
Richman
J J
JJ
Eiden
H L
HL
Spiegelberg
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Raz
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood* / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology; D016466:CHO Cells; D006224:Cricetinae; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D004926:Escherichia coli / Q000201:enzymology; D005260:Female; D015483:HIV Antibodies / Q000097:blood* / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology*; D007111:Immunity, Cellular / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000276:immunology*; D010957:Plasmids / Q000276:immunology; D012967:Sodium Dodecyl Sulfate; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D013873:Thionucleotides / Q000276:immunology*; D013997:Time Factors; D001616:beta-Galactosidase / Q000235:genetics / Q000276:immunology*
D000907:Antibodies, Bacterial; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D007074:Immunoglobulin G; D009838:Oligodeoxyribonucleotides; D013873:Thionucleotides; D012967:Sodium Dodecyl Sulfate; D007371:Interferon-gamma; D001616:beta-Galactosidase