Making a better DNA vaccine by raising the alarm

Unlike most vaccines, which help protect you from a microbe before you’re infected, DNA vaccines have the potential to treat diseases that already have taken root, including different types of cancer.

Published in the journal Cancer Research, scientists at the University of Pennsylvania have now found a new way to make these vaccines more effective.

Conceptually, DNA vaccines are pretty simple. When cells take up this new DNA, the body starts making the corresponding protein, which the immune system will recognize as foreign — and then launch its attack. But getting them to work well is far trickier.

David Weiner, professor of pathology and laboratory medicine at the University of Pennsylvania, has been studying DNA vaccines for more than 20 years.

“There have been about 30,000 people who have been tested with DNA vaccines, and they’ve had a great safety profile,” said Weiner, a pioneer in the field. “But they have not been as immune-potent as we would like — until very, very recently, through a combination of approaches.”

Weiner, who has tested his latest DNA vaccine for cancer treatment in mice, found that the addition of another DNA — which makes a communication molecule called an alarmin — significantly amped up the immune response.

“We’ve taken that natural warning system and applied it now to a cancer model,” said Weiner. “And so we’re calling the immune system and sort of reprogramming it through this feature to protect against these latent tumor cells.”

For the mice in Weiner’s lab, the added DNA was transformative.

“Animals that were vaccinated with this gene adjuvant as part of the vaccine cleared tumors much faster, and, basically, all of the animals cure their tumors,” he said.

Weiner attributes the success to the alarmin’s ability to spur killer T cells into action — a “holy grail” for vaccine designers. The strategy might also be useful for other cancers and chronic viral diseases, although each will have to be tested.

For now, Weiner is focused on cervical cancer. Even though the newest HPV vaccines are highly effective, they are only helpful in preventing the disease. “Cervical cancer remains the second-largest cancer killer of women worldwide, with several hundred thousand deaths every year,” he said.

If further testing in animals goes well, Weiner said the first-stage clinical trials for people might happen within the next several years.