TY - JOUR
T1 - Induction of anti-simian immunodeficiency virus cellular and humoral immune responses in rhesus macaques by peptide immunogens
T2 - Correlation of CTL activity and reduction of cell-associated but not plasma virus load following challenge
AU - Vogel, T. U.
AU - Beer, B. E.
AU - Zur Megede, J.
AU - Ihlenfeldt, H. G.
AU - Jung, G.
AU - Holzammer, S.
AU - Watkins, D. I.
AU - Altman, J. D.
AU - Kurth, R.
AU - Norley, S.
PY - 2002
Y1 - 2002
N2 - 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-1/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.
AB - 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-1/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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U2 - 10.1099/0022-1317-83-1-81
DO - 10.1099/0022-1317-83-1-81
M3 - Article
C2 - 11752704
AN - SCOPUS:0036138290
VL - 83
SP - 81
EP - 91
JO - Journal of General Virology
JF - Journal of General Virology
SN - 0022-1317
IS - 1
ER -