Novel HIV-1 clade B candidate vaccines designed for HLA-B*5101(+) patients protected mice against chimaeric ecotropic HIV-1 challenge.
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.
Roshorm
Yaowaluck
Y
Weatherall Institute of Molecular Medicine, University of Oxford, The John Radcliffe, UK.
Hong
Jessie P
JP
Kobayashi
Naoki
N
McMichael
Andrew J
AJ
Volsky
David J
DJ
Potash
Mary Jane
MJ
Takiguchi
Masafumi
M
Hanke
Tomás
T
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D004274:DNA, Recombinant / Q000235:genetics; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D015685:Fusion Proteins, gag-pol / Q000235:genetics / Q000276:immunology; D015488:HIV Antigens / Q000235:genetics / Q000276:immunology; D016655:HIV Core Protein p24 / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D015235:HLA-B Antigens / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology
D016915:AIDS Vaccines; D004274:DNA, Recombinant; D000939:Epitopes; D015685:Fusion Proteins, gag-pol; D015488:HIV Antigens; D016655:HIV Core Protein p24; D015235:HLA-B Antigens; D014409:Tumor Necrosis Factor-alpha; D054301:gag Gene Products, Human Immunodeficiency Virus; C054858:p17 protein, Human Immunodeficiency Virus Type 1; C514799:p24 protein, Human Immunodeficiency Virus Type 1; D007371:Interferon-gamma