DNA Vaccination

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DNA plasmid expression vectors can be used for gene transfer. Generally, the transgene is placed downstream of a strong promoter, such as the heterologous cytomegalovirus promoter/

enhancer region, and upstream of a polyadenylation signal sequence, to allow for appropriate RNA processing and transport from the nucleus. Transfection of cells with such plasmid DNA can effect high-level expression of the transgene, provided the RNA has appropriate Kozak sequences for initiating effective translation of the RNA into protein (37).

This technique is currently being explored as a potential strategy for treating CLL and other B-cell malignancies. For patients with B-cell tumors, the immunoglobulin idiotype expressed by the neoplastic clone provides a defined tumor-specific target antigen. However, the immunoglobulin idiotype is poorly immunogenic, especially in patients with CLL. Fusion of a gene encoding a fragment of tetanus toxin with the gene encoding the idiotype can enhance the immune response to such weak tumor-specific antigens. DNA fusion vaccines containing genes that encode immune-enhancing factors can also augment the immune response to such antigens (38-40).

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