Abstract
Human immunodeficiency virus (HIV)-1 Tat protein induces protection in non-human primates upon systemic vaccination. In view of the design of mucosal vaccines against HIV-1 we studied the immune response to native Tat (aa 1-86) in mice following intranasal delivery of the protein with two mucosal adjuvants, Escherichia coli heat-labile enterotoxin (LT) and LT-R72, a non-toxic mutant of LT. Immunization with Tat and the two adjuvants induced in BALB/c but not in C57BL/6 mice high and persistent levels of serum IgG and secretory IgA in vaginal and intestinal fluids. Mice sera neutralized Tat and recognized two epitopes mapping in the regions 1-20 and 46-60. Furthermore, their splenocytes proliferated and secreted IFN-gamma and IL-6 in response to Tat. Finally, CTLs were also elicited and they recognized an epitope localized within aa 11-40 of Tat.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adjuvants, Immunologic / pharmacology
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Administration, Intranasal
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Amino Acid Sequence
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Animals
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Bacterial Toxins / pharmacology
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Cell Division / physiology
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Cytokines / biosynthesis
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Enterotoxins / pharmacology
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Enzyme-Linked Immunosorbent Assay
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Epitope Mapping
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Escherichia coli Proteins*
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Female
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Gene Products, tat / administration & dosage
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Gene Products, tat / immunology*
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HIV Antibodies / biosynthesis*
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Humans
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Immunity, Mucosal / immunology*
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Immunoglobulin A / biosynthesis*
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Immunoglobulin A / immunology*
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Immunoglobulin G / biosynthesis
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Immunoglobulin G / blood
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Intestines / 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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Molecular Sequence Data
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Neutralization Tests
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T-Lymphocytes, Cytotoxic / immunology
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T-Lymphocytes, Cytotoxic / physiology*
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Vagina / immunology
Substances
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Adjuvants, Immunologic
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Bacterial Toxins
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Cytokines
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Enterotoxins
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Escherichia coli Proteins
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Gene Products, tat
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HIV Antibodies
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Immunoglobulin A
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Immunoglobulin G
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heat-labile enterotoxin, E coli