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Systemic mobilization of antigen presenting cells, with a chimeric Flt-3 and G-CSF receptor agonist, during immunization of Macaca mulatta with HIV-1 antigens is insufficient to modulate immune responses or vaccine efficacy.

Abstract
In order to improve the efficacy of current vaccine candidates against HIV/AIDS, we sought to strengthen the induction of immune responses via simultaneous in vivo mobilization of dendritic cells using a chimeric Flt-3 and G-CSF receptor agonists (ProGP). We investigated ProGP treatment in combination with two DNA immunizations encoding HIV-Env89.6, SIV-Gag proteins to increase the priming of immune responses. Administration of this Flt-3/G-CSF chimera elicited marked increases in numbers of both plasmacytoid and myeloid dendritic cells. However, there was no increase seen in T-cell responses either directly following the DNA immunization or after further boosting with MVA vectors expressing HIV-Env89.6p, SIV-Gag. After challenge with SHIV89.6p all animals became infected and no differences were seen between the ProGP treated versus the control group with regard to plasma virus load or CD4 T-cell count. We conclude that besides mobilization of dendritic cells additional stimuli to induce dendritic cell maturation may be needed for avid boosting of antigen specific immune activation.
AuthorsGerrit Koopman, D Mortier, H Niphuis, Ann M Farese, Larry E Kahn, Dean Mann, Ralf Wagner, Thomas J MacVittie, Susan L Woulfe, Jonathan L Heeney
JournalVaccine (Vaccine) Vol. 23 Issue 33 Pg. 4195-202 (Jul 21 2005) ISSN: 0264-410X [Print] Netherlands
PMID15896883 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • AIDS Vaccines
  • Antibodies, Viral
  • HIV Antigens
  • Proto-Oncogene Proteins
  • Receptors, Granulocyte Colony-Stimulating Factor
  • Recombinant Fusion Proteins
  • FLT3 protein, human
  • Receptor Protein-Tyrosine Kinases
  • fms-Like Tyrosine Kinase 3
Topics
  • AIDS Vaccines (administration & dosage, genetics, immunology)
  • Animals
  • Antibodies, Viral (blood)
  • Antigen-Presenting Cells
  • Dendritic Cells (drug effects, immunology)
  • HIV Antigens (administration & dosage)
  • HIV Infections (immunology, prevention & control)
  • HIV-1 (chemistry, immunology)
  • Humans
  • Immunity (drug effects)
  • Immunization
  • Macaca mulatta
  • Proto-Oncogene Proteins (agonists, genetics, immunology)
  • Receptor Protein-Tyrosine Kinases (genetics, immunology)
  • Receptors, Granulocyte Colony-Stimulating Factor (agonists)
  • Recombinant Fusion Proteins (immunology)
  • fms-Like Tyrosine Kinase 3

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