Therapeutic dendritic-cell vaccine for chronic HIV-1 infection.
We present the results of a preliminary investigation of the efficacy of a therapeutic dendritic cell (DC)-based vaccine for HIV-1. We immunized 18 chronically HIV-1-infected and currently untreated individuals showing stable viral loads for at least 6 months with autologous monocyte-derived DCs loaded with autologous aldrithiol-2-inactivated HIV-1. Plasma viral load levels were decreased by 80% (median) over the first 112 d following immunization. Prolonged suppression of viral load of more than 90% was seen in 8 individuals for at least 1 year. The suppression of viral load was positively correlated with HIV-1-specific interleukin-2 or interferon-gamma-expressing CD4(+) T cells and with HIV-1 gag-specific perforin-expressing CD8(+) effector cells, suggesting that a robust virus-specific CD4(+) T-helper type 1 (T(H)1) response is required for inducing and maintaining virus-specific CD8(+) effectors to contain HIV-1 in vivo. The results suggest that inactivated whole virus-pulsed DC vaccines could be a promising strategy for treating people with chronic HIV-1 infection.
Lu
Wei
W
Institut de Recherche sur les Vaccins et l'Immunothérapie des Cancers et du Sida, Laboratoire d'Oncologie et Virologie Moléculaire, Faculté de Médecine René Descartes, Centre Biomédical des Saints-Pères, Université Paris 5, France. louis.wei-lu@irvics.org
Arraes
Luiz Claudio
LC
Ferreira
Wylla Tatiana
WT
Andrieu
Jean-Marie
JM
D015082:2,2'-Dipyridyl / Q000031:analogs & derivatives*; D016915:AIDS Vaccines / Q000276:immunology / Q000627:therapeutic use*; D000328:Adult; D001938:Brazil; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D004220:Disulfides; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy* / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000097:blood; D008562:Membrane Glycoproteins / Q000378:metabolism; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D013997:Time Factors; D019562:Viral Load
D016915:AIDS Vaccines; D004220:Disulfides; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; C001105:2,2'-dipyridyl disulfide; D015082:2,2'-Dipyridyl; D007371:Interferon-gamma