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Animal: RNA Viruses |
Paul Ehrlich Institute, 63225 Langen, Germany1
Institut für Organische Chemie, University of Tübingen, 72076 Tübingen, Germany2
Wisconsin Regional Primate Research Center, University of Wisconsin, Madison, WI 53715-1299, USA3
Emory University Vaccine Center at Yerkes, Atlanta, GA 30329, USA4
Author for correspondence: Stephen Norley. Present address: Robert Koch-Institut, Nordufer 20, 13353 Berlin, Germany. Fax +49 30 4547 2914. e-mail NorleyS{at}rki.de
Lipopeptides which carry the N-terminal moiety tripalmitoyl-S-glyceryl-cysteinyl-seryl-seryl (P3CSS) 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 SIVmac 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 MID50 of the homologous, uncloned SIVmac251-32H 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.
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