The Emerging Role of DNA Vaccines

W. Michael McDonnell, MD, Western Washington Medical Group, and Frederick K. Askari, MD, PhD, University of Michigan.

Disclosures
In This Article

How DNA Vaccines Work

Immunizing the host with a piece of viral DNA rather than an antigenic protein fragment of the virus, helps to stimulate the generation of cell-mediated immunity (Fig. 2). DNA vaccines contain the nucleotides encoding an antigenic portion of the virus such as the viral core region or envelope region. The DNA is taken up into the host cell, translated, and the protein product expressed. Viral protein is made intracellularly and the protein is processed via the endogenous MHC class I pathway.

DNA vaccines. DNA vaccines favor a cell-mediated immune response. DNA plasmid vector vaccines carry the genetic information encoding an antigen, allowing the antigen to be produced inside of a host cell, leading to a cell-mediated immune response via the MHC I pathway. The plasmid DNA vaccine (above) carries the genetic code for a piece of pathogen or tumor antigen. The plasmid vector is taken up into cells and transcribed in the nucleus (1). The single stranded mRNA (2) is translated into protein in the cytoplasm. The DNA vaccine-derived protein antigen (3) is then degraded by proteosomes into intracellular peptides (4). The vaccine derived-peptide binds MHC class I molecules (5). Peptide antigen/MHC I complexes are presented on the cell surface (6), binding cytotoxic CD 8+ lymphocytes, and inducing a cell-mediated immune response. Because DNA vaccines generate cell-mediated immunity, the hope is that they will be effective against some difficult viruses even as standard vaccines have failed to work.

More specifically, the plasmid DNA vaccine carries the genetic code for a segment of pathogen or tumor antigen. The plasmid vector is taken up into cells and transcribed in the nucleus. The single stranded mRNA is translated into protein in the cytoplasm. The DNA vaccine-derived protein antigen is then degraded by proteosomes into intracellular peptides. The vaccine-derived peptide binds MHC class I molecules. Peptide antigen/MHC I complexes are presented on the cell surface where they bind cytotoxic CD 8+ lymphocytes and induce a cell-mediated immune response. Because DNA vaccines generate cell- mediated immunity, the hope is that they will be effective against some difficult viruses -- even when standard vaccines have failed to work.

DNA vaccines may have significant advantages over standard vaccines. They can express antigenic epitopes which more closely resemble native viral epitopes and could therefore be more effective. With live attenuated vaccines and killed vaccines the manufacturing process can alter the secondary and tertiary structure of the proteins and therefore the antigenicity of the vaccine; with naked DNA vaccines the host cell is manufacturing the viral epitope. DNA vaccines would be safer than live virus vaccines, especially in immunocompromised patients, such as those infected with HIV.[12]DNA vaccines may be constructed to include genes against several different pathogens, thus decreasing the number of vaccinations necessary to fully immunize children. Construction and manufacture of DNA vaccines would be simple. Finally DNA vaccines may hold promise in treating those already infected with chronic viral infections (ie, HCV, HIV or HSV).[13]

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