title: HIV-Specific CD4(+) and CD8(+) immune responses are generated with a gp120-depleted, whole-killed HIV-1 immunogen with CpG immunostimulatory sequences of DNA.
abstract: We examined the adjuvant effects of a synthetic CpG oligodeoxynucleotide immunostimulatory sequence (ISS) using a whole-killed, gp120-depleted HIV antigen (HIV-1 antigen) in a Lewis rat model. We hypothesized that HIV-1-specific CD4(+) T helper (Th) immune responses could be enhanced when an ISS was combined with an HIV-1 antigen in incomplete Freund's adjuvant (IFA). We also reasoned that if such Th responses were sufficient, such a combination might also induce HIV-specific CD8(+) T cell immune responses. Here we demonstrate that the HIV-1 antigen in IFA combined with ISS stimulates both CD4(+) and CD8(+) HIV-specific immune responses as measured by interferon-gamma (IFN-gamma) in the ELISPOT assay. A strong correlation between these CD4(+) and CD8(+) responses was demonstrated. Furthermore, we found that the HIV-1 antigen in IFA with ISS as an adjuvant stimulated strong antibody responses to core antigen (p24). These studies suggest that the combination of the whole-killed, gp120-depleted HIV-1 antigen in IFA with ISS may be an ideal candidate to test in nonhuman primates and in human studies as a preventive HIV-1 vaccine.
authors.affiliation: The Immune Response Corporation, Carlsbad, CA 92008, USA. shotdoc@imnr.com
authors.forename: R B
authors.initials: RB
authors.lastname: Moss
authors.forename: J
authors.initials: J
authors.lastname: Diveley
authors.forename: F C
authors.initials: FC
authors.lastname: Jensen
authors.forename: E
authors.initials: E
authors.lastname: Gouveia
authors.forename: J
authors.initials: J
authors.lastname: Savary
authors.forename: D J
authors.initials: DJ
authors.lastname: Carlo
mesh_terms: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018899:CpG Islands / Q000276:immunology*; D004279:DNA, Viral / Q000276:immunology; D005620:Freund's Adjuvant / Q000276:immunology; D015488:HIV Antigens / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015497:HIV-1 / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D023421:Models, Animal; D051381:Rats; D011917:Rats, Inbred Lew; D014613:Vaccines, Attenuated
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D004279:DNA, Viral; D015488:HIV Antigens; D015699:HIV Envelope Protein gp120; D014613:Vaccines, Attenuated; D007371:Interferon-gamma; D005620:Freund's Adjuvant