Abstract
Novel candidate HIV-1 vaccines have been constructed, which are tailor-designed for HLA-B*5101(+) patients infected with HIV-1 clade B. These vaccines employ novel immunogen HIVB-B*5101 derived from consensus HIV-1 clade B Gag p17 and p24 regions coupled to two Pol-derived B*5101-restricted epitopes, which are together with a third B*5101 epitope in Gag dominant in HIV-1-infected long-term non-progressing patients. Both plasmid DNA and modified vaccinia virus Ankara (MVA) vectors supported high expression levels of the HIVB-B*5101 immunogen in cultured cells. Heterologous DNA prime-recombinant MVA boost regimen induced efficiently HIV-1-specific CD8(+) T-cell responses in BALB/c mice. These vaccine-elicited T cells were multifunctional, killed efficiently target cells in vivo, and protected mice against challenge with ecotropic HIV-1/NL4-3 and ecotropic HIV-1/NDK chimaeric viruses with HIV-1 clade B or D backbones, respectively, and ecotropic murine leukemia virus gp80 envelope, and therefore did so in the absence of anti-HIV-1 gp120 antibodies. These results support further development of HIVB-B*5101 vaccines in combined heterologous-modality regimens. The use of allele-specific vaccines in humans is discussed in the context of other developments in the HIV-1 field.
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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AIDS Vaccines / administration & dosage
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AIDS Vaccines / genetics
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AIDS Vaccines / immunology*
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Amino Acid Sequence
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Animals
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Blotting, Western
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CD8-Positive T-Lymphocytes / cytology
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / metabolism
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DNA, Recombinant / genetics
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Epitopes / genetics
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Epitopes / immunology
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Female
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Flow Cytometry
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Fusion Proteins, gag-pol / genetics
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Fusion Proteins, gag-pol / immunology
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HIV Antigens / genetics
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HIV Antigens / immunology
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HIV Core Protein p24 / genetics
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HIV Core Protein p24 / immunology
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HIV Infections / immunology*
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HIV Infections / prevention & control
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HIV Infections / virology
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HIV-1 / genetics
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HIV-1 / immunology*
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HLA-B Antigens / immunology*
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Humans
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Interferon-gamma / metabolism
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Mice
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Mice, Inbred BALB C
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Mice, Inbred CBA
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Tumor Necrosis Factor-alpha / metabolism
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gag Gene Products, Human Immunodeficiency Virus / genetics
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gag Gene Products, Human Immunodeficiency Virus / immunology
Substances
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AIDS Vaccines
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DNA, Recombinant
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Epitopes
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Fusion Proteins, gag-pol
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HIV Antigens
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HIV Core Protein p24
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HLA-B Antigens
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Tumor Necrosis Factor-alpha
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gag Gene Products, Human Immunodeficiency Virus
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p17 protein, Human Immunodeficiency Virus Type 1
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p24 protein, Human Immunodeficiency Virus Type 1
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Interferon-gamma