title: Vaccination with gp120-depleted HIV-1 plus immunostimulatory CpG oligodeoxynucleotides in incomplete Freund's adjuvant stimulates cellular and humoral immunity in rhesus macaques.
abstract: Whole killed human immunodeficiency virus type 1 (HIV-1) immunogens contain the more conserved epitopes of HIV-1 and therefore may provide some utility as potential HIV-1 vaccine candidates. Previous studies have shown that synthetic oligodeoxynucleotides (ODN) containing unmethylated cytosine-guanine (CpG) dinucleotides trigger rapid stimulation of both CD4+ and CD8+ T cells. Here, we investigated whether immunization of rhesus macaques with an inactivated gp120-depleted HIV-1 immunogen, emulsified in incomplete Freund's adjuvant (IFA) together with immunostimulatory CpG-containing ODN (ODN 2006), would elicit HIV-specific cellular and humoral immune responses. High titer anti-p24 antibody levels were induced in all four immunized animals that were sustained 6 weeks after the fifth and final boost at 23 months. These anti-gag antibodies mapped to linear B-cell epitopes within the matrix (MA), capsid (CA), p2, nucleocapsid (NC) and p6 proteins of HIV-1 gag. HIV-specific interferon-gamma-producing CD4+ and CD8+ T-cell responses were measured before and after the fourth and fifth immunizations by both intracellular cytokine (ICC) and ELISPOT techniques; responses were detected in three of the four immunized animals. CD4+ T-cell epitopes appear to map within amino acids 261-290 and 291-320 of p24 CA protein. Immunizations were well tolerated both locally and systemically. Based on these results, further studies of this approach are warranted.
authors.affiliation: Infectious Disease Research Department, Southern Research Institute, 431 Aviation Way, Frederick, MD 21701, USA. silvera@sri.org
authors.forename: Peter
authors.initials: P
authors.lastname: Silvera
authors.forename: Jay R
authors.initials: JR
authors.lastname: Savary
authors.forename: Virginia
authors.initials: V
authors.lastname: Livingston
authors.forename: Jessica
authors.initials: J
authors.lastname: White
authors.forename: Kelledy H
authors.initials: KH
authors.lastname: Manson
authors.forename: Michael H
authors.initials: MH
authors.lastname: Wyand
authors.forename: Peter L
authors.initials: PL
authors.lastname: Salk
authors.forename: Ronald B
authors.initials: RB
authors.lastname: Moss
authors.forename: Mark G
authors.initials: MG
authors.lastname: Lewis
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D000917:Antibody Formation; D018899:CpG Islands / Q000276:immunology*; D005620:Freund's Adjuvant / Q000276:immunology; D015483:HIV Antibodies / Q000096:biosynthesis; D015699:HIV Envelope Protein gp120 / Q000235:genetics*; D015658:HIV Infections / Q000276:immunology* / Q000517:prevention & control; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000276:immunology; D008253:Macaca mulatta; D014611:Vaccination
chemical_list: D016915:AIDS Vaccines; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D007371:Interferon-gamma; D005620:Freund's Adjuvant