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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.

Original publication

DOI

10.1002/eji.200939309

Type

Journal article

Journal

Eur J Immunol

Publication Date

07/2009

Volume

39

Pages

1831 - 1840

Keywords

AIDS Vaccines, Amino Acid Sequence, Animals, Blotting, Western, CD8-Positive T-Lymphocytes, DNA, Recombinant, Epitopes, Female, Flow Cytometry, Fusion Proteins, gag-pol, HIV Antigens, HIV Core Protein p24, HIV Infections, HIV-1, HLA-B Antigens, Humans, Interferon-gamma, Mice, Mice, Inbred BALB C, Mice, Inbred CBA, Tumor Necrosis Factor-alpha, gag Gene Products, Human Immunodeficiency Virus