Abstract
Vaccination against visceral leishmaniasis has received limited attention compared with cutaneous leishmaniasis, although the need for an effective vaccine against visceral leishmaniasis is pressing. In this study, we demonstrate for the first time that a recombinant stage-specific hydrophilic surface protein of Leishmania donovani, recombinant hydrophilic acylated surface protein B1 (HASPB1), is able to confer protection against experimental challenge. Protection induced by rHASPB1 does not require adjuvant and, unlike soluble Leishmania Ag + IL-12, extends to the control of parasite burden in the spleen, an organ in which parasites usually persist and are refractory to a broad range of immunological and chemotherapeutic interventions. Both immunohistochemistry (for IL-12p40) and enzyme-linked immunospot assay (for IL-12p70) indicate that immunization with rHASPB1 results in IL-12 production by dendritic cells, although an analysis of Ab isotype responses to rHASPB1 suggests that this response is not sufficient in magnitude to induce a polarized Th1 response. Although both vaccinated and control-infected mice have equivalent frequencies of rHASPB1-specific CD4(+) T cells producing IFN-gamma, vaccine-induced protection correlates with the presence of rHASPB1-specific, IFN-gamma-producing CD8(+) T cells. Thus, we have identified a novel vaccine candidate Ag for visceral leishmaniasis, which appears to operate via a mechanism similar to that previously associated with DNA vaccination.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Protozoan / biosynthesis
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Antigens, Protozoan / administration & dosage
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Antigens, Protozoan / genetics
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Antigens, Protozoan / immunology
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CD8-Positive T-Lymphocytes / immunology
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Cells, Cultured
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Dendritic Cells / immunology
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Dendritic Cells / metabolism
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Drug Combinations
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Female
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Injections, Subcutaneous
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Interferon-gamma / biosynthesis
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Interleukin-12 / administration & dosage
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Interleukin-12 / biosynthesis
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Interleukin-12 / immunology
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Interleukin-4 / biosynthesis
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Leishmania donovani / genetics
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Leishmania donovani / growth & development
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Leishmania donovani / immunology*
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Leishmaniasis, Visceral / immunology
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Leishmaniasis, Visceral / parasitology
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Leishmaniasis, Visceral / prevention & control*
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Liver Diseases, Parasitic / immunology
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Liver Diseases, Parasitic / parasitology
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Liver Diseases, Parasitic / prevention & control
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Lymphocyte Activation
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Membrane Proteins / administration & dosage
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Membrane Proteins / genetics
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Membrane Proteins / immunology*
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Mice
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Mice, Inbred BALB C
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Protozoan Proteins / administration & dosage
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Protozoan Proteins / genetics
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Protozoan Proteins / immunology*
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Protozoan Vaccines / administration & dosage
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Protozoan Vaccines / genetics
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Protozoan Vaccines / immunology*
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Recombinant Proteins / administration & dosage
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Recombinant Proteins / immunology*
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Solubility
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Spleen / cytology
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Spleen / immunology
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Spleen / metabolism
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Splenic Diseases / immunology
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Splenic Diseases / parasitology
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Splenic Diseases / prevention & control
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Th2 Cells / immunology
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Th2 Cells / metabolism
Substances
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Antibodies, Protozoan
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Antigens, Protozoan
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Drug Combinations
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Membrane Proteins
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Protozoan Proteins
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Protozoan Vaccines
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Recombinant Proteins
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Interleukin-12
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Interleukin-4
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Interferon-gamma