Abstract
Among candidate antigens for human immunodeficiency virus (HIV) prophylactic vaccines, the regulatory protein Tat is a critical early target, but has a potential for immune suppression. Adenovirus (Ad) recombinants encoding wild-type HIV Tat (Tat-wt) and a transdominant negative mutant HIV Tat (Tat22) were constructed and administered to mice separately or together with Ad-SIVgag. Immunogenicity and effects on immune responses to the co-administered Gag immunogen were evaluated. Wild-type and mutant Tat recombinants elicited similar Tat-specific cellular and humoral immune responses. Co-administration of either Tat immunogen with Ad-SIVgag induced modest but significant enhancement of Gag-specific interferon-gamma secreting T cells and lymphoproliferative responses. Neither the Ad-recombinant encoding Tat-wt nor Tat22 suppressed induction of anti-Tat or anti-Gag antibodies. Based on the immune responses observed in mice, both recombinants appear to be suitable vaccine candidates. Their contribution to protective efficacy remains to be determined in a non-human primate model.
Publication types
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Research Support, N.I.H., Intramural
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Research Support, Non-U.S. Gov't
MeSH terms
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AIDS Vaccines / administration & dosage
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AIDS Vaccines / genetics
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AIDS Vaccines / immunology
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Adenoviridae / genetics
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Adenoviridae / immunology
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Animals
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Antibodies, Viral / biosynthesis
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Base Sequence
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DNA, Recombinant / genetics
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Female
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Gene Products, gag / genetics*
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Gene Products, gag / immunology*
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Gene Products, tat / genetics*
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Gene Products, tat / immunology*
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Genes, gag
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Genes, tat
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Genetic Vectors
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HIV Antibodies / biosynthesis
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HIV-1 / genetics*
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HIV-1 / immunology*
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Humans
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Immunity, Cellular
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Immunization
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Interferon-gamma / biosynthesis
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Macaca mulatta
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Mice
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Mice, Inbred BALB C
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Mutation
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Simian Immunodeficiency Virus / genetics*
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Simian Immunodeficiency Virus / immunology*
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T-Lymphocytes / immunology
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Vaccines, Synthetic / administration & dosage
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Vaccines, Synthetic / genetics
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Vaccines, Synthetic / immunology
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tat Gene Products, Human Immunodeficiency Virus
Substances
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AIDS Vaccines
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Antibodies, Viral
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DNA, Recombinant
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Gag protein p27, Simian immunodeficiency virus
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Gene Products, gag
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Gene Products, tat
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HIV Antibodies
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Vaccines, Synthetic
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tat Gene Products, Human Immunodeficiency Virus
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Interferon-gamma