Enhanced HIV-1 specific immune response by CpG ODN and HIV-1 immunogen-pulsed dendritic cells confers protection in the Trimera murine model of HIV-1 infection.
We have recently developed a novel small animal model for HIV-1 infection (Ayash-Rashkovsky et al., http://www.fasebj.org/cgi/doi/10.1096/fj.04-3184fje; doi:10.1096/fj.04-3184fje). The mice were successfully infected with HIV-1 for 4-6 wk with different clades of either T- or M-tropic isolates. HIV-1 infection was accompanied by rapid loss of human CD4+ T cells, decrease in CD4/CD8 ratio, and increased T cell activation. HIV specific human humoral and cellular immune responses were observed in all HIV-1 infected animals. In the present study, HIV specific human immune responses, both humoral and cellular, were generated in noninfected Trimera mice, after their immunization with gp120-depleted HIV-1 antigen, presented by autologous human dendritic cells. Addition of CpG ODN to the antigen-pulsed DCs significantly enhanced (by 2- to 30-fold) the humoral and cellular HIV-1 specific immune responses. Only mice immunized with the HIV-1 immunogen and CpG were completely protected from infection with HIV-1 after challenge with high infection titers of the virus. This novel small animal model for HIV-1 infection may thus serve as an attractive platform for rapid testing of candidate HIV-1 vaccines and of adjuvants and may shorten the time needed for the development and final assessment of protective HIV-1 vaccines in human trials.
Ayash-Rashkovsky
Mila
M
Hebrew University Hadassah Medical School, Jerusalem, Israel.
Borkow
Gadi
G
Davis
Heather L
HL
Moss
Ronald B
RB
Moss
Ronnald B
RB
Bartholomew
Richard
R
Bentwich
Zvi
Z
D016915:AIDS Vaccines / Q000276:immunology*; D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control*; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D003713:Dendritic Cells / Q000276:immunology*; D004195:Disease Models, Animal; D015483:HIV Antibodies / Q000097:blood; D016655:HIV Core Protein p24 / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D018418:Th2 Cells / Q000276:immunology; D051194:Toll-Like Receptor 1 / Q000032:analysis
D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D015483:HIV Antibodies; D016655:HIV Core Protein p24; D009838:Oligodeoxyribonucleotides; D051194:Toll-Like Receptor 1; D007371:Interferon-gamma