IMMUNE RESPONSE--ANTIGEN BEARING DENDRITIC CELLS IN HIV

Rockefeller University, New York NY

Investigators

Linked publications & trials

Abstract

Overview: Despite the marked success of highly active antiretroviral therapy (HAART) against HIV infection in containing plasma viremia and lowering viral load, the long-term effects and efficacy of the multidrug regimens are unknown. A long-lived viral reservoir has been identified within resting CD4+ T cells, providing a safe haven for the virus during seemingly effective therapy, making eradication of HIV difficult if not impossible. Cytotoxic T lymphocyte (CTL) responses against HIV, which are felt to be essential for immune control of the infection, have been noted to decrease in most patients who are on effective HAART, probably because of lack of antigenic stimulation. This decrease in the anti-HIV immune response may account for the rapid rebound of plasma viremia usually seen with interruption of HAART. Thus, the patients who are seemingly "doing well", (maintaining undetectable viral loads) may be the ones most in need of boosting of the immune surveillance against HIV. Our laboratory has demonstrated that an effective way to generate antigen-specific CTLs is by using dendritic cells (DCs) as antigen presenting cells. We have developed methods for obtaining these cells in large numbers from blood monocytes maturing them ex vivo to enhance their function. In our first clinical study, we found that a single injection of antigen-bearing mature DCs rapidly and dramatically boosted antigen-specific CD4 and CD8 T cell immunity in humans. Furthermore, booster injections induced rapid anamnestic responses. In this study, we will examine whether DCs bearing HIV antigens can boost CD4 and CD8 responses against HIV in infected individuals who are maintaining undetectable viral loads on HAART. A subsequent goal is to determine whether immunized individuals can suppress rebound viremia upon discontinuation of HAART. Hypothesis: Dendritic cells pulsed with HIV antigens boost T cell immunity in HLA A*0201+HIV-seropositive patients.