An effective immune response to simian immunodeficiency virus (SIV) can be elicited in vivo by a new therapeutic dendritic-cell (DC) vaccine, as reported by Lu and colleagues in Nature Medicine.

Chronic infection with HIV or SIV results in progressive immunodeficiency and ineffective antiviral immune responses. Although highly active antiretroviral therapy (HAART) can reduce the viral load and improve CD4+ T-cell counts, these drugs do not restore immune functions completely, and a therapeutic vaccine is highly sought after. Previous studies have shown that DCs that have been pulsed with chemically (aldrithiol-2, AT-2)-inactivated HIV or SIV can stimulate the activity of antiviral cytotoxic T lymphocytes (CTLs) in vitro. Here, Lu and colleagues test the activity of an AT-2-inactivated SIV-pulsed DC vaccine in vivo in SIV-infected rhesus monkeys.

Fourteen SIV-infected monkeys were split into two groups of vaccinated (ten) and control (four) animals. Vaccinated monkeys received immunizations and boosters of AT-2-inactivated SIV-loaded DCs, whereas control monkeys received comparable injections of unloaded autologous DCs. Levels of SIV cellular DNA and plasma RNA decreased rapidly in the vaccinated animals, and the levels remained low and stable for the remainder of the study. In addition, vaccination led to higher numbers of CD4+ T cells and increased titres of neutralizing antibodies. In the control animals, the levels of viraemia, CD4+ T cells and antibodies remained unchanged throughout the study.

Next, the authors assessed SIV-specific immunity. Higher numbers of SIV-specific memory T cells could be detected after vaccination, the cytolytic activity of SIV-specific CTLs was increased and the inhibitory effect of CD8+ T cells on replication of SIV was enhanced.

Secondary lymph nodes are important sites for the replication of SIV and HIV, and for the development of antiviral responses. Lymph-node biopsies carried out in the last week of the study showed that the lymphoid follicular DC network was destroyed in half of the control monkeys, whereas it was intact in all of the vaccinated monkeys. Also, the levels of cellular SIV DNA and SIV RNA were considerably lower in the vaccinated monkeys than in the control monkeys. Most importantly, high levels of lymph-node SIV-specific CTLs were associated with low levels of local cellular SIV burden, illustrating the effective control of viral spread by cell-mediated immunity in situ.

This study shows that inactivated SIV-pulsed DC-based vaccines can elicit effective cellular and humoral immune responses against SIV in vivo, resulting in the control of SIV replication in secondary lymphoid tissues and reduced levels of viraemia in vaccinated monkeys. If this approach could be adapted for use in humans, then inactivated whole-virus DC vaccines could be promising therapies for controlling chronic infection with HIV.