[LbOr11] Safety, immunogenicity and antiviral efficacy of a new topical DNA vaccine in macaques with chronic infection and AIDS

14th International AIDS Conference

Barcelona, Spain — July 7-12, 2002

[TITLE:] Safety, immunogenicity and antiviral efficacy of a new topical DNA vaccine in macaques with chronic infection and AIDS

[AUTHOR(S):] Julianna Lisziewicz, Jianqing Xu, Jeffrey Trocio, Lucia Whitman, Franco Lori¹, Mark Lewis²

Int Conf AIDS. 2002 Jul 7-12;14:Abstract No. LbOr11

BACKGROUND: Several studies have demonstrated that vigorous HIV-specific T cell immune responses can suppress virus replication and eliminate HIV-infected cells. These findings provided the rationale for the development of therapeutic vaccines.

METHODS: We showed that a novel topical DNA vaccine (DermaVirtm) could transduce epidermal Langerhans cells, prompt them to migrate to the lymph node, mature to SIV/HIV antigen-expressing dendritic cells and elicit potent HIV-specific T cell immunity. To study the effect of DermaVir therapy we conducted two separate studies on 26 chronically SIV₂₅₁-infected rhesus macaques and an additional 10 macaques already showing signs of AIDS. Monkeys were randomized to receive HAART, STI (3 weeks on HAART & 3 weeks off), STI+DermaVir and DermaVir alone.

RESULTS: Unlike 7 chronically infected animals receiving STI alone, the 7 randomized to receive STI+DermaVir progressively controlled viral rebound during treatment interruptions from a median 33,860 copies/ml to <200 copies/ml. Six macaques treated with DermaVir alone experienced no increase in viral load and survived longer than the untreated controls. The macaques with AIDS started the STI+DermaVir treatment with a significantly higher viral load and suppressed viral rebound from a median 4,292,260 to <200 copies/mL. Control of viral load in the absence of therapy was associated with augmented SIV-specific CD8 and CD4 T cells as measured by IFN-γ intracellular cytokine assay. DermaVir therapy did not show signs of toxic side effects.

CONCLUSIONS: These primate trials constitute the first evidence of the antiviral efficacy of a therapeutic vaccine measured by viral load suppression during treatment interruption and delayed disease progression. The simplicity of the DNA formulation and topical application, as well as the antiviral potency and safety of DermaVir, make it a very attractive vaccine for the treatment of HIV/AIDS.

Presenting author: Julianna Lisziewicz

1Research Institute for Genetic and Human Therapy.

2Address missing from original.

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