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.
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.
Koopman
Gerrit
G
Biomedical Primate Research Center, Department of Virology, Lange Kleiweg 139, 2288 GJ Rijswijk, The Netherlands. koopman@bprc.nl
Mortier
D
D
Niphuis
H
H
Farese
Ann M
AM
Kahn
Larry E
LE
Mann
Dean
D
Wagner
Ralf
R
MacVittie
Thomas J
TJ
Woulfe
Susan L
SL
Heeney
Jonathan L
JL
D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000938:Antigen-Presenting Cells; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D015488:HIV Antigens / Q000008:administration & dosage*; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control; D015497:HIV-1 / Q000737:chemistry / Q000276:immunology; D006801:Humans; D007109:Immunity / Q000187:drug effects*; D007114:Immunization; D008253:Macaca mulatta; D011518:Proto-Oncogene Proteins / Q000819:agonists* / Q000235:genetics / Q000276:immunology; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000276:immunology; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000819:agonists*; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D051941:fms-Like Tyrosine Kinase 3
D016915:AIDS Vaccines; D000914:Antibodies, Viral; D015488:HIV Antigens; D011518:Proto-Oncogene Proteins; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D011993:Recombinant Fusion Proteins; C497970:FLT3 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3