Therapeutic Dendritic-Cell Vaccine for Simian AIDS

Wei Lu, Xiaoxian Wu, Yaozeng Lu, Weizhong Guo, Jean-Marie Andrieu

Disclosures

Nat Med. 2003;9(1) 

In This Article

Abstract and Introduction

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 immunodeficiency viruses.

The lack of functional virus-specific effector T lymphocytes and neutralizing antibodies is a key immunogical feature of chronic human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infections.[1,2,3,4,5,6] Dendritic cells (DCs) are essential for initiating and maintaining virus-specific cellular immunity.[5] Previous studies have shown that DCs cultured from the peripheral blood of HIV-negative donors or SIV-negative animals and pulsed with chemically (2,2'-dithiodipyridine or aldrithiol-2[8] (AT-2) inactivated HIV or SIV were potent stimulators of primary major histocompatibility complex (MHC) class-I-restricted T-cell responses in vitro.[9,10] On the other hand, DCs cultured from the peripheral blood monocytes of HIV-infected patients[11,12,13] or SIV-infected animals[10] have also been shown to be potent stimulators of memory HIV/SIV-specific cytotoxic T lymphocytes (CTLs) in vitro. We have previously demonstrated that DCs of HIV-infected patients pulsed with AT-2-inactivated autologous HIV elicited functional virus-specific effector CD8+ T lymphocytes that were capable of eradicating HIV-infected cells in vitro through a MHC class-I-restricted CTL-mediated killing mechanism.[14] Here we explore the in vivo effect of an AT-2-inactivated virus-pulsed DC vaccine using the SIV-infected rhesus monkey model.

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