Potency of cell-mediated immune responses to different combined HIV-1 immunogens in a humanized murine model.
In this study, cell-mediated immune responses were evaluated in HLA-A2.1 mice that received polycistronic vector expressing HIV-1 gp120, gag and pol or single vectors expressing gp120 + gag/pol as well as recombinant structural proteins and adjuvants. Mice primed with the polycistronic DNA/CpG and boosted with the same regimen plus proteins induced a higher T-cell proliferative response to gp120. However, a very high frequency of IFN-gamma was detected in mice receiving the mixture of gp120 + gag/pol DNA constructs, recombinant proteins and CpG. We also measured specific CD8+T cells in PBMCs by intracellular cytokine and HLA-A2.1-peptide dimer staining in response to HLA-A2.1-restricted HIV-1 epitopes (gp120, gag and pol). The group that received single gp120 + gag/pol DNA constructs, recombinant proteins and CpG had a higher CD8+T cell response to the combination of peptides compared to the other groups that received the polycistronic construct. The present study reveals an optimal combination of immunogens to enhance immune responses against HIV-1.
Azizi
Ali
A
Infectious Disease and Vaccine Research Center, Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.
Ghorbani
Masoud
M
Kryworuchko
Marko
M
Aucoin
Susan
S
Diaz-Mitoma
Francisco
F
D016915:AIDS Vaccines / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016466:CHO Cells; D006224:Cricetinae; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D004279:DNA, Viral / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D015684:Gene Products, pol / Q000276:immunology; D015488:HIV Antigens / Q000276:immunology*; D016655:HIV Core Protein p24 / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D007115:Immunization Schedule; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018448:Models, Immunological; D010455:Peptides / Q000276:immunology; D010957:Plasmids / Q000235:genetics; D014162:Transfection; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology
D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D016207:Cytokines; D004279:DNA, Viral; D015684:Gene Products, pol; D015488:HIV Antigens; D016655:HIV Core Protein p24; D015699:HIV Envelope Protein gp120; D015789:HLA-A2 Antigen; D010455:Peptides; D014614:Vaccines, Synthetic