Novel HIV-1 clade B candidate vaccines designed for HLA-B*5101(+) patients protected mice against chimaeric ecotropic HIV-1 challenge

Eur J Immunol. 2009 Jul;39(7):1831-40. doi: 10.1002/eji.200939309.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • AIDS Vaccines / administration & dosage
  • AIDS Vaccines / genetics
  • AIDS Vaccines / immunology*
  • Amino Acid Sequence
  • Animals
  • Blotting, Western
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • DNA, Recombinant / genetics
  • Epitopes / genetics
  • Epitopes / immunology
  • Female
  • Flow Cytometry
  • Fusion Proteins, gag-pol / genetics
  • Fusion Proteins, gag-pol / immunology
  • HIV Antigens / genetics
  • HIV Antigens / immunology
  • HIV Core Protein p24 / genetics
  • HIV Core Protein p24 / immunology
  • HIV Infections / immunology*
  • HIV Infections / prevention & control
  • HIV Infections / virology
  • HIV-1 / genetics
  • HIV-1 / immunology*
  • HLA-B Antigens / immunology*
  • Humans
  • Interferon-gamma / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred CBA
  • Tumor Necrosis Factor-alpha / metabolism
  • gag Gene Products, Human Immunodeficiency Virus / genetics
  • gag Gene Products, Human Immunodeficiency Virus / immunology

Substances

  • AIDS Vaccines
  • DNA, Recombinant
  • Epitopes
  • Fusion Proteins, gag-pol
  • HIV Antigens
  • HIV Core Protein p24
  • HLA-B Antigens
  • Tumor Necrosis Factor-alpha
  • gag Gene Products, Human Immunodeficiency Virus
  • p17 protein, Human Immunodeficiency Virus Type 1
  • p24 protein, Human Immunodeficiency Virus Type 1
  • Interferon-gamma