Targeting cell-free HIV and virally-infected cells with anti-HLA-DR immunoliposomes containing amphotericin B

Objective: To evaluate the ability of liposomes bearing anti-HLA-DR Fab' fr agments (immunoliposomes) and containing amphotericin B (AmB) to target and neutralize cell-free HIV-1 particles and virally-infected cells. Methods: The effect of AmB on the attachment and fusion of HIV-1(NL4-3) to Jurkat E6.1 cells has been evaluated using a p24 enzymatic assay. The abili ty of AmB to inhibit HIV-l-based luciferase reporter viruses pseudotyped wi th HXB2, AML-V and VSV-G envelopes has been evaluated in jurkat E6.1 cells. The efficacy of free and immunoliposomal AmB to inhibit cell-free HIV, tha t have incorporated or not HLA-DR molecules, has been evaluated in HLA-DR/n egative (NEG) 1G5 T cells and HLA-DR/positive (POS) Mono Mac 1 cells. Results: AmB inhibited HIV infectivity independently of the nature of viral envelope proteins. Pretreatment of HIV with AmB had no major effect on vir al attachment and fusion process to jurkat E6.1 cells. Immunoliposomal AmB (0.5 mug/ml) led to a 77% inhibition of replication of HLA-DR/POS HIV-1 wit h no cell toxicity, whereas free AmB had no significant antiviral activity at this concentration. A complete inhibition of viral replication was obser ved following incubation of viruses with immunoliposomal AmB (2.5 mug/ml). Anti-HLA-DR immunoliposomes containing AmB, had no effect on the infectivit y of HLA-DR/NEG HIV-1 particles in HLA-DR/NEG T lymphoid cells but complete ly inhibited replication of viruses in an HLA-DR/POS monocytic cell line. Conclusion: The incorporation of neutralizing agents in anti-HLA-DR immunol iposomes could represent a novel therapeutic strategy to specifically targe t cell-free HIV particles and virally-infected cells to treat HIV infection more efficiently. (C) 2000 Lippincott Williams & Wilkins.