Dendritic-cell vaccine elicits strong anti-SIV response in monkeys
In monkeys infected with simian immunodeficiency virus (SIV), vaccination with inactivated SIV-pulsed dendritic cells dramatically reduces SIV DNA and RNA levels, according to a report published in the 23 December online issue of Nature Medicine.
“This work demonstrates for the first time an effective and durable therapeutic vaccine for treating simian AIDS, which opens the possibility of treating human AIDS by vaccination,” lead author Dr Wei Lu, from the Universite Rene Descartes in Paris, said in a statement.
The vaccine is created by harvesting dendritic cells from an infected animal and then treating the cells with a chemically inactivated form of SIV. These cells are then reintroduced into the animal to stimulate an enhanced anti-SIV response.
Previous reports have shown that pulsed dendritic cells can elicit a strong antiviral response in vitro. But until now, the efficacy of this technique in vivo has not been known.
In the current study, Dr Lu’s team inoculated 14 rhesus monkeys with SIV. A few weeks later, 10 of the animals began receiving injections of inactivated SIV-pulsed dendritic cells. The four remaining animals received injections that contained non-pulsed dendritic cells.
By six weeks, monkeys treated with the pulsed cells had experienced a 50- and 1000-fold decrease in SIV DNA and RNA levels, respectively. Moreover, these reduced levels persisted for the remaining 34 weeks of the study. In contrast, no changes in SIV DNA or RNA levels were noted in the control group.
Further analysis of lymph node lymphocytes from the pulsed cell-treated animals revealed an inverse relationship between SIV DNA and RNA levels and SIV-specific T-cell responses, the authors note.
In contrast to highly active antiretroviral therapy (HAART), “therapeutic dendritic cell vaccines have no systemic side effects and need only a few subcutaneous injections,” Dr Lu noted.
Dr Lu said that his team is currently preparing phase I/II clinical trial that “will tell us, within two years, whether a similar success can be reached in HIV-infected people.” Also, “our research is now focused on improving these therapeutic vaccines in the monkey model with the ultimate aim of ‘immunologic eradication’ of SIV/HIV.”
Lu W, Wu X, Lu Y et al. Therapeutic dendritic-cell vaccine for simian AIDS. Nat Med 2002 Dec 23; [epub ahead of print]