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

T. U. Vogel, B. E. Beer, J. Zur Megede, H. G. Ihlenfeldt, G. Jung, S. Holzammer, David Watkins, J. D. Altman, R. Kurth, S. Norley

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)81-91
Number of pages11
JournalJournal of General Virology
Volume83
Issue number1
StatePublished - Jan 15 2002
Externally publishedYes

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Simian Immunodeficiency Virus
Humoral Immunity
Macaca mulatta
Cellular Immunity
Lipopeptides
Epitopes
Viruses
Peptides
Haplorhini
Viral RNA
Virus Diseases
Viral Load
Cell Count
T-Lymphocytes
Infection

ASJC Scopus subject areas

  • Virology
  • Immunology

Cite this

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. / Vogel, T. U.; Beer, B. E.; Zur Megede, J.; Ihlenfeldt, H. G.; Jung, G.; Holzammer, S.; Watkins, David; Altman, J. D.; Kurth, R.; Norley, S.

In: Journal of General Virology, Vol. 83, No. 1, 15.01.2002, p. 81-91.

Research output: Contribution to journalArticle

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abstract = "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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