title: Immunization with gp120-depleted whole killed HIV immunogen and a second-generation CpG DNA elicits strong HIV-specific responses in mice.
abstract: HIV-1 Immunogen is a gp120-depleted whole killed virus vaccine candidate formulated with Incomplete Freund's Adjuvant (HIV-IFA). We evaluated in a mouse model the immunogenicity of HIV-IFA by itself and when combined with HYB2055, an immunomodulatory oligonucleotide consisting of a novel DNA structure and synthetic CpR immunostimulatory motif, as an adjuvant. C57/BL6 mice were immunized with HIV-IFA alone or combined with HYB2055. Mice treated with HYB2055 or with PBS were used as controls. Compared to HIV-IFA alone, immunization with HIV-IFA and HYB2055 combination elicited strong production of HIV- and p24-specific IFNgamma, RANTES, MIP 1alpha, and MIP 1beta, as well as high titers of HIV- and p24-specific antibodies. Inclusion of HYB2055 also reduced levels of IL-5 produced by HIV-IFA alone. HYB2055 enhances the immunogenicity of HIV-IFA and shifts responses towards a type 1 cytokine profile. The immune enhancing effects of HYB2055 adjuvant were dose-dependent. These findings warrant clinical evaluation of the HIV-1 immunogen/HYB2055 candidate as a therapeutic vaccine for HIV-1 infected patients.
authors.affiliation: Chair of Immunology, DISP LITA Vialba, Via GB Grassi 74, 20157 Milano, Italy.
authors.forename: Daria
authors.initials: D
authors.lastname: Trabattoni
authors.forename: Alberto
authors.initials: A
authors.lastname: Clivio
authors.forename: Dorothy H
authors.initials: DH
authors.lastname: Bray
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Bhagat
authors.forename: Silvia
authors.initials: S
authors.lastname: Beltrami
authors.forename: Giada
authors.initials: G
authors.lastname: Maffeis
authors.forename: Eugenio
authors.initials: E
authors.lastname: Cesana
authors.forename: Peter
authors.initials: P
authors.lastname: Lowry
authors.forename: Francesca
authors.initials: F
authors.lastname: Lissoni
authors.forename: Ekambar R
authors.initials: ER
authors.lastname: Kandimalla
authors.forename: Timothy
authors.initials: T
authors.lastname: Sullivan
authors.forename: Sudhir
authors.initials: S
authors.lastname: Agrawal
authors.forename: Richard
authors.initials: R
authors.lastname: Bartholomew
authors.forename: Mario
authors.initials: M
authors.lastname: Clerici
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D002478:Cells, Cultured; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000096:biosynthesis; D016207:Cytokines; D004359:Drug Therapy, Combination; D005260:Female; D015483:HIV Antibodies / Q000097:blood; D015699:HIV Envelope Protein gp120; D007371:Interferon-gamma / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D008214:Lymphocytes / Q000276:immunology; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D009841:Oligonucleotides / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D016915:AIDS Vaccines; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D016207:Cytokines; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C098825:HIV-1 immunogen, incomplete Freund's adjuvant; C506514:HYB-2055; D015848:Interleukin-5; D019402:Macrophage Inflammatory Proteins; D009841:Oligonucleotides; D007371:Interferon-gamma