1. ^*Research Institute for Genetic and Human Therapy (RIGHT), Washington, District of Columbia, USA
2. Research Institute for Genetic Immunity, LLC Washington, District of Columbia, USA
3. ^†PolyPlus-Transfection, Illkirch, France
4. ^‡Molecular Histology Labs Inc., Gaithersburg, Maryland, USA
5. ^§Advanced BioScience Laboratories Inc., Rockville, Maryland, USA
6. ^¶National Institutes of Health, National Cancer Institute, Bethesda, Maryland, USA
7. ^#Laboratoire de Chimie Genetique, Faculté de Pharmacie, Illkirch, France

Correspondence: Julianna Lisziewicz, Research Institute for Genetic and Human Therapy (RIGHT), Washington, District of Columbia 20007, USA. Email: lisziewj@geneticimmunity.com

Received 22 December 2003; Revised 30 June 2004; Accepted 20 July 2004; Published online 21 December 2004.

Abstract

Human immunodeficiency virus (HIV) vaccines have the potential to improve antiretroviral drug treatment by inducing cytotoxic killing of HIV-infected cells. Prophylactic vaccines utilize new antigens to initiate immunity; however, in HIV-infected individuals the load of viral antigen is not the limiting factor for the restoration of immune responses. Here we describe a novel immunization strategy with DermaVir that improves viral antigen presentation using dendritic cells (DC). DermaVir contains a distinctive plasmid DNA expressing all HIV proteins except integrase to induce immune responses with broad specificity. The DNA is formulated to a mannosilated particle to target antigen-presenting cells and to protect the DNA from intracellular degradation. After topical application, DermaVir-transduced cells migrate from the skin to the draining lymph node and interdigitate as DermaVir-expressing, antigen-presenting DC. We compared the immunogenicity of topical and ex vivo DC-based DermaVir vaccinations in naïve rhesus macaques. Both vaccinations induced simian immunodeficiency virus-specific CD4 helper and CD8 memory T cells detected by an in vivo skin test and an in vitro intracellular cytokine-based assay. Topical DermaVir vaccination represents an improvement upon existing ex vivo DC-based immunization technologies and may provide a new therapeutic option for HIV-infected patients.