Optimization of DNA vaccines through the use of molecular adjuvants.

Although the injection of DNA into tissues was originally reported in the 1950s, the technology has gained more attention in recent years as a safe means of mimicking in vivo protein production normally associated with natural infection (1-3). Nucleic acid or DNA inoculation is an important vaccination technique that delivers DNA constructs encoding specific immunogens directly into the host (4-11). These expression cassettes transfect the host cells, which become the in vivo protein source for the production of antigen. This antigen then is the focus of the resulting immune response. This vaccination technique is being explored as an immunization strategy against a variety of infectious diseases as well as cancer.

Genetic vaccination targeting T-cell receptors.

T-cell antigen receptor (TCR) genes (which consist of variable (V), diversity (D), joining (J) and constant (C) segments) undergo rearrangement during T-cell development and result in the expression of a disulfide linked heterodimer (α and ß chains) on the surface of mature T-cells (1,2). The TCR confers specificity to each T-cell for antigen recognition (in the context of major histocompatibility (MHC) molecules (1,3). Clonal TCR-ß chain gene rearrangements have been demonstrated in DNA samples derived from cutaneous tumors, peripheral blood lymphocytes and lymph nodes of patients with cutaneous T cell lymphomas (CTCL) (4-6). Together with immunohistologic data (7), these findings indicate that CTCL is a clonal disease of malignant T cells that express α/ß-TCR.