title: Selective induction of cell-mediated immunity and protection of rhesus macaques from chronic SHIV(KU2) infection by prophylactic vaccination with a conserved HIV-1 envelope peptide-cocktail.
abstract: Infection of Indian-origin rhesus macaques by the simian human immunodeficiency virus (SHIV) is considered to be a suitable preclinical model for directly testing efficacy of vaccine candidates based on the HIV-1 envelope. We used this model for prophylactic vaccination with a peptide-cocktail comprised of highly conserved HIV-1 envelope sequences immunogenic/antigenic in macaques and humans. Separate groups of macaques were immunized with the peptide-cocktail by intravenous and subcutaneous routes using autologous dendritic cells (DC) and Freund's adjuvant, respectively. The vaccine elicited antigen specific IFN-gamma-producing cells and T-cell proliferation, but not HIV-neutralizing antibodies. The vaccinated animals also exhibited efficient cross-clade cytolytic activity against target cells expressing envelope proteins corresponding to HIV-1 strains representative of multiple clades that increased after intravenous challenge with pathogenic SHIV(KU2). Virus-neutralizing antibodies were either undetectable or present only transiently at low levels in the control as well as vaccinated monkeys after infection. Significant control of plasma viremia leading to undetectable levels was achieved in majority of vaccinated monkeys compared to mock-vaccinated controls. Monkeys vaccinated with the peptide-cocktail using autologous DC, compared to Freund's adjuvant, and the mock-vaccinated animals, showed significantly higher IFN-gamma production, higher levels of vaccine-specific IFN-gamma producing CD4(+) cells and significant control of plasma viremia. These results support DC-based vaccine delivery and the utility of the conserved HIV-1 envelope peptide-cocktail, capable of priming strong cell-mediated immunity, for potential inclusion in HIV vaccination strategies.
authors.affiliation: Department of Veterinary Sciences, The University of Texas M. D. Anderson Cancer Center, Bastrop, TX 78602, USA.
authors.forename: Pramod N
authors.initials: PN
authors.lastname: Nehete
authors.forename: Bharti P
authors.initials: BP
authors.lastname: Nehete
authors.forename: Lori
authors.initials: L
authors.lastname: Hill
authors.forename: Pallavi R
authors.initials: PR
authors.lastname: Manuri
authors.forename: Veerabhadran
authors.initials: V
authors.lastname: Baladandayuthapani
authors.forename: Lei
authors.initials: L
authors.lastname: Feng
authors.forename: Johnny
authors.initials: J
authors.lastname: Simmons
authors.forename: K Jagannadha
authors.initials: KJ
authors.lastname: Sastry
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology / Q000627:therapeutic use*; D000595:Amino Acid Sequence; D000818:Animals; D002908:Chronic Disease; D017124:Conserved Sequence; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology*; D018449:SAIDS Vaccines / Q000276:immunology / Q000627:therapeutic use*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology / Q000627:therapeutic use; D054299:env Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments; D018449:SAIDS Vaccines; D014614:Vaccines, Synthetic; D054299:env Gene Products, Human Immunodeficiency Virus; D007371:Interferon-gamma