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Therapeutic dendritic-cell vaccine for simian AIDS

Abstract

An effective immune response against human immunodeficiency virus or simian immunodeficiency virus (SIV) is critical in achieving control of viral replication. Here, we show in SIV-infected rhesus monkeys that an effective and durable SIV-specific cellular and humoral immunity is elicited by a vaccination with chemically inactivated SIV-pulsed dendritic cells. After three immunizations made at two-week intervals, the animals exhibited a 50-fold decrease of SIV DNA and a 1,000-fold decrease of SIV RNA in peripheral blood. Such reduced viral load levels were maintained over the remaining 34 weeks of the study. Molecular and cellular analyses of axillary and inguinal node lymphocytes of vaccinated monkeys revealed a correlation between decreased SIV DNA and RNA levels and increased SIV-specific T-cell responses. Neutralizing antibody responses were augmented and remained elevated. Inactivated whole virus-pulsed dendritic cell vaccines are promising means to control diseases caused by immuno- deficiency viruses.

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Figure 1: Morphology and phenotype of macaque monocyte-derived DCs.
Figure 2: Virologic and immunologic monitoring in immunized and non-immunized macaques.
Figure 3: SIV-specific CTL and anti-SIV activity of peripheral T cells.
Figure 4: Histopathology of macaque LN.
Figure 5: Virologic and immunologic analysis in macaque LN.

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Acknowledgements

We thank L. Cao, W. Deng, D. Han, H. Luo, J. Ma, S. Yang, J. Yuan, F. Zhang, W. Zhang, J. Zeng and Y. Zhou for assistance, and Air France for its prestige travel assistance. This study was supported by the Institut de Recherche sur les Vaccins et l'Immunothérapie des Cancers et du Sida (IRVICS).

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Correspondence to Wei Lu.

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Lu, W., Wu, X., Lu, Y. et al. Therapeutic dendritic-cell vaccine for simian AIDS. Nat Med 9, 27–32 (2003). https://doi.org/10.1038/nm806

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