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.
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.
Vogel
Thorsten U
TU
Wisconsin Regional Primate Research Center, University of Wisconsin, Madison, WI 53715-1299, USA3.|Paul Ehrlich Institute, 63225 Langen, Germany1.
Beer
Brigitte E
BE
Paul Ehrlich Institute, 63225 Langen, Germany1.
Zur Megede
Jan
J
Paul Ehrlich Institute, 63225 Langen, Germany1.
Ihlenfeldt
Hans-Georg
HG
Institut für Organische Chemie, University of Tübingen, 72076 Tübingen, Germany2.
Jung
Günther
G
Institut für Organische Chemie, University of Tübingen, 72076 Tübingen, Germany2.
Holzammer
Silke
S
Paul Ehrlich Institute, 63225 Langen, Germany1.
Watkins
David I
DI
Wisconsin Regional Primate Research Center, University of Wisconsin, Madison, WI 53715-1299, USA3.
Altman
John D
JD
Emory University Vaccine Center at Yerkes, Atlanta, GA 30329, USA4.
Kurth
Reinhard
R
Paul Ehrlich Institute, 63225 Langen, Germany1.
Norley
Stephen
S
Paul Ehrlich Institute, 63225 Langen, Germany1.
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
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