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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-specifc interleukin-2 or interferon-γ-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 (TH1) 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.

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Figure 1: Immunologic and virologic evolution of the 18 immunized participants.
Figure 2: Intracellular cytokine detection of T cells following stimulation with AT-2-inactivated HIV-1-pulsed DC (patient 13).
Figure 3: HIV-1-specfic T-cell immunity in the 18 immunized patients.
Figure 4: HIV-1-gag tetramer staining and intracellular perforin detection in gated CD3+CD8+ cells.
Figure 5: HIV-1 gag–specific perforin-expressing CD8+ T cells (effectors) in 10 immunized HLA A*0201-positive individuals.


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We acknowledge L. Lapa who performed leukapheresis; M.F. and M.M. Costa Mendes who provided assistance to patients; C. Padilha for clinical assistance; J.L. de Lima Filho who provided administrative support; H. Gozard, V. Jagot, A. Tiafvoon and J. Yuan for technical assistance; and Air France for its travel assistance. This study was supported by the Institut de Recherche sur les Vaccins et l'Immunothérapie des Cancers et du Sida (IRVICS), the Association de Recherche sur les Maladies Tumorales et Virales (AREMAS), the Instituto de Pesquisa en Immunoterapia de Pernambuco (IPIPE), and the Assitance Publique—Hôpitaux de Paris. We would like to express our gratitude to D. Skigin (1956–2003) for his donation.

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Correspondence to Wei Lu or Jean-Marie Andrieu.

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Supplementary information

Supplementary Fig. 1

Flow cytometry analysis of inactivated virus-pulsed DCs. (PDF 130 kb)

Supplementary Fig. 2

Predictive markers for the viral-load response. (PDF 111 kb)

Supplementary Table 1

Quality control of DC vaccine by flow cytometry (PDF 82 kb)

Supplementary Table 2

Quality control of DC vaccine by ICC (PDF 83 kb)

Supplementary Table 3

Individual plasma viral load evolution (PDF 79 kb)

Supplementary Table 4

Individual CD4+ T-cell evolution (PDF 77 kb)

Supplementary Table 5

Individual anti-HIV antibody titers (PDF 68 kb)

Supplementary Table 6

Individual HIV-1-specific TH1 cytokine evolution (PDF 86 kb)

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Lu, W., Arraes, L., Ferreira, W. et al. Therapeutic dendritic-cell vaccine for chronic HIV-1 infection. Nat Med 10, 1359–1365 (2004).

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