286-W.
A Novel Topical DNA Vaccine (DermaVir) for the Induction of T-Cell Immunity
J. Lisziewicz*1, J. Xu1, J. Trocio1, L. Whitman1, P. Markham2, S. Arya3, J-P. Behr4, and F. Lori1
1Res. Inst. for Genetic and Human Therapy (RIGHT), Washington, DC; 2Advanced BioSci. Labs. Inc., Rockville, MD; 3NCI, NIH, Bethesda, MD; and 4Faculte de Pharmacie, Illkirch, France

Background: We have recently described induction of potent Th-1 polarized HIV-specific T cell immunity by ex vivo cultured autologous genetically-modified dendritic cells (DC) in macaques. Here we describe a similarly effective vaccination based on in vivo genetic manipulation of DC.
Methods: We developed a practical, non-invasive, transcutaneous gene transfer technology to genetically engineer large numbers of lymph node DC in order to induce potent T-cell-mediated immune responses. A plasmid DNA encoding replication and integration defective SHIV was constructed to allow safe and efficient expression of most viral proteins and authentic presentation of viral antigens. The DNA vaccine, DermaVir, was formulated with mannosylated polyethylenimine in an aqueous glucose solution and applied on the surface of shaved skin to transduce Langerhans cells in the epidermis.
Results: DNA-expressing Langerhans cells migrated to the T-cell area of the draining lymph node, interdigitated as DC and presented DNA-derived antigens to T cells. The unprecedented high efficacy of this approach was demonstrated in both mice and macaques where 0.025 mg DNA applied on the skin resulted in ca. 20,000 gene-expressing DC in the draining lymph node. An average of 3800 SIV-specific IFN-gamma expressing CD8+ T cells per 106 CD8+ T cells were detected as early as 3 weeks after one DermaVir immunization of 4 macaques. Prior to vaccination the same macaques had undetectable immune responses. Antibody response was absent after 3 subsequent DermaVir applications and no adverse events were reported.
Conclusions: We developed a novel topical DNA vaccine to induce T-cell responses specific to the DNA-derived antigens. This DNA vaccine is a promising candidate for testing in humans because: it induces Th-1 polarized T cell-mediated immune responses in macaques; large-scale manufacture is straight forward; it requires a small dose of DNA (0.025 mg); and application is topical, painless and requires no needles.

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Ez egy előadásabsztrakt, egy újfajta gyógyszerről. És az elsőszámú szerző J.Lisziewicz tényleg magyar, Lisziewicz Julianna. Nemrég tartott egy előadást Budapesten. Lehet, hogy erről van szó.