Gene Vaccines[dhelix]

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   Figure 1. Newly synthesized viral protein in the cytoplasm of an infected cell is degraded into peptides that are transported into the endoplasmic reticulum and then to the Golgi apparatus. Peptides bind to newly synthesized major histocompatibility complex class I molecules; the complex is then expressed on the surface of the cell where, in the presence of appropriate accessory molecules, binding to the T-cell receptor of CD8 cells can occur. This binding results in activation of the cytolytic T lymphocyte. Adapted from McDonnell and Askari , with permission from the Massachusetts Medical Society. Activation of cytolytic T lymphocytes.+(2)
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   Figure 2. . Survival rates among mice immunized against influenza by using a DNA vaccine encoding the nucleoprotein of influenza from the 1934 H1N1 strain ( ). When infected with a lethal dose of influenza from a strain different from the strain from which the vaccine was made, immunized mice had a higher survival rate than did control mice immunized with a control ( ). This protection was mediated by cytolytic T lymphocytes that recognized portions of the nucleoprotein. . The strains from which the DNA vaccine was made ( ) and used to infect ( ) the mice. The influenza nucleoprotein was more highly conserved than the surface proteins. Reproduced with permission from the British Society for Immunology. Donnelly JJ, Ulmer JB, Liu MA. Immunization with polynucleotides. Immunology. 1994; 2:20-6. Heterosubtypic protection.TopsquarescirclesBottomleftright
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   Figure 3. Studies in bone marrow chimeric mice demonstrated that after immunization with plasmid DNA encoding an antigen, cytolytic T lymphocytes were activated by antigen-presenting cells ( ) that either had been directly transfected by the DNA or had received antigen via cross-priming, in which a non–antigen-presenting cell initially produces the protein encoded by the DNA vaccine, then transfers the antigen in some form to a professional antigen-presenting cell for generation of MHC class I restricted cytolytic T cells. Production of the protein antigen in non–antigen-presenting cells, such as myocytes, cannot result in direct stimulation of cytolytic T cells . Mechanism of antigen presentation for generation of cytolytic T cells after DNA vaccination.APC(3)
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   Figure 4. Sites within a DNA plasmid can be altered to potentially increase the potency of or alter the type of immune responses induced by the DNA vaccine. BGH = bovine growth hormone; CMVintA = cytomegalovirus promoter with the intron A sequence; mRNA = messenger RNA. Designer gene vaccines.

• Copyright ©2004 by the American College of Physicians