Therapeutic dendritic-cell vaccine for chronic HIV-1 infection

Abstract

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-specific interleukin-2 or interferon-gamma-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 (T(H)1) 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.

Phenotypic and Functional Analysis of Immune CD8+ T Cell Responses Induced by a Single Injection of a HIV DNA Vaccine in Mice

“…Remarkably, with CD4 ϩ T cell help, the CD8 effector activity was maintained (35). Similar data were reported for HIV-1 infection showing that HIV-specific CD4 ϩ T cells can sustain and restore HIV-1-specific CD8 ϩ T cell function in HIV-1-infected patients (36,37). These data clearly show the CD4 ϩ T cell dependence of CD8 ϩ T cells for the induction and maintenance of fully functional CD8 ϩ T cell response.…”

To kill or be killed: how HIV exhausts the immune system

“…This is suggested by a recent study showing that immunization of HIV-infected patients with dendritic cells loaded with chemically inactivated HIV could induce, in the absence of antiretroviral therapy, a prolonged suppression of HIV viral load, which was positively correlated with virus-specific CD4 and CD8 T cells. 175 This study shows for the first time that improved immune control of HIV infection is possible and it offers new hopes of the possibility of therapeutic vaccines to modulate the course of HIV disease.…”

DNA Vaccines: Progress and Challenges

“…However, the duration of immune responses were short, and various adjuvants to genetic immunization appear necessary. Lu et al (75) treated HIV-infected patients with their own dendritic cells, cultured and matured ex vivo, pulsed with the patients' own inactivated viral strain and then given back to the patient. In half of these individuals, virological control was obtained for several months without antiviral chemotherapy.…”