title: Induction of anti-simian immunodeficiency virus cellular and humoral immune responses in rhesus macaques by peptide immunogens: correlation of CTL activity and reduction of cell-associated but not plasma virus load following challenge.
abstract: Lipopeptides which carry the N-terminal moiety tripalmitoyl-S-glyceryl-cysteinyl-seryl-seryl (P(3)CSS) have been shown to have effective adjuvant and transmembrane carrier properties. To test the ability of these constructs to immunize against simian immunodeficiency virus [(SIV)(mac)] infection, rhesus macaques, prescreened for expression of the Mamu-A*01 MHC class I molecule, were immunized at regular intervals with lipopeptides corresponding to known SIV(mac) CTL epitopes alone or in combination with multiple antigenic peptides corresponding to neutralizing epitopes. Both humoral and CTL responses were elicited and the monkeys, along with non-immunized control animals, were challenged intravenously with 20 MID(50) of the homologous, uncloned SIV(mac251-32H) grown in rhesus monkey PBMC. Although none of the monkeys were protected from infection, most demonstrated an anamnestic CTL response with epitope-specific CTL precursor frequencies reaching as high as 1 in 20 total PBMC as measured by limiting dilution CTL assay or 25% of all CD8(+) T-cells using tetrameric MHC-I/peptide complexes. A significant inverse correlation between the levels of CTLp and the number of infected cells in circulation was observed. However, no such correlation with the plasma viral load (RNA copies/ml) was evident.
authors.affiliation: Wisconsin Regional Primate Research Center, University of Wisconsin, Madison, WI 53715-1299, USA3.|Paul Ehrlich Institute, 63225 Langen, Germany1.
authors.forename: Thorsten U
authors.initials: TU
authors.lastname: Vogel
authors.affiliation: Paul Ehrlich Institute, 63225 Langen, Germany1.
authors.forename: Brigitte E
authors.initials: BE
authors.lastname: Beer
authors.affiliation: Paul Ehrlich Institute, 63225 Langen, Germany1.
authors.forename: Jan
authors.initials: J
authors.lastname: Zur Megede
authors.affiliation: Institut für Organische Chemie, University of Tübingen, 72076 Tübingen, Germany2.
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Ihlenfeldt
authors.affiliation: Institut für Organische Chemie, University of Tübingen, 72076 Tübingen, Germany2.
authors.forename: Günther
authors.initials: G
authors.lastname: Jung
authors.affiliation: Paul Ehrlich Institute, 63225 Langen, Germany1.
authors.forename: Silke
authors.initials: S
authors.lastname: Holzammer
authors.affiliation: Wisconsin Regional Primate Research Center, University of Wisconsin, Madison, WI 53715-1299, USA3.
authors.forename: David I
authors.initials: DI
authors.lastname: Watkins
authors.affiliation: Emory University Vaccine Center at Yerkes, Atlanta, GA 30329, USA4.
authors.forename: John D
authors.initials: JD
authors.lastname: Altman
authors.affiliation: Paul Ehrlich Institute, 63225 Langen, Germany1.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Kurth
authors.affiliation: Paul Ehrlich Institute, 63225 Langen, Germany1.
authors.forename: Stephen
authors.initials: S
authors.lastname: Norley
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D000917:Antibody Formation; D000956:Antigens, Viral / Q000276:immunology*; D007111:Immunity, Cellular; D008074:Lipoproteins / Q000276:immunology*; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology; D018449:SAIDS Vaccines / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000097:blood / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology*; D019562:Viral Load
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D008074:Lipoproteins; D010455:Peptides; D018449:SAIDS Vaccines; D014614:Vaccines, Synthetic; C061893:N-palmitoyl-5,6-dipalmitoyl-S-glycerylcysteinyl-seryl-serine