DNA vaccines boosted by dendritic cells

The concept sounds ideal: vaccines made of DNA that could be taken in by other cells and give instructions for how to fight off different diseases. The reality, however, has fallen short. Although DNA vaccines have been around for about 15 years and shown lots of promise for HIV, SARS and influenza vaccines during preclinical testing in mice, researchers have yet to make them potent enough to be helpful in humans.

Now, Rockefeller University researchers believe they may have a fix: targeting HIV antibody proteins directly to the coordinating cells of the immune system.

Ralph Steinman, Henry G. Kunkel Professor and head of the Laboratory of Cellular Physiology and Immunology, is using dendritic cells to capitalize on the potential of DNA vaccines. Dendritic cells, which Steinman codiscovered in 1973, are responsible for directing the immune system's response to disease. So Godwin Nchinda, a postdoc in Steinman's lab, and their European colleagues developed a DNA vaccine that works by instructing cells to produce HIV antibody proteins aimed at dendritic cells.

Current DNA vaccines require multiple, high-dose administrations to even begin to have an immune effect. But when the researchers injected the dendritic-cell targeted DNA vaccine into mice, they created a vaccine that appeared to be much more efficient in just one application. "We decreased the dose of DNA needed to immunize a mouse by about 100 times," Steinman says.

Because DNA vaccines are already approved for use in people, Steinman believes that the new dendritic-cell approach could be quickly extended to testing in humans. "A better DNA vaccine could help the entire HIV research field, especially if it could be used in combination with other vaccines."

Journal of Clinical Investigation 118(4): 1427?1436 (April 1, 2008)

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