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DNA Drugs Come of Age

After years of false starts, a new generation of DNA vaccines and medicines for HIV, influenza and other stubborn illnesses is now in clinical trials
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In a head-to-head competition held 10 years ago, scientists at the National Institutes of Health tested two promising new types of vaccine to see which might offer the strongest protection against one of the deadliest viruses on earth, the human immunodeficiency virus (HIV) that causes AIDS. One vaccine consisted of DNA rings called plasmids, each carrying a gene for one of five HIV proteins. Its goal was to get the recipient’s own cells to make the viral proteins in the hope they would provoke protective reactions by immune cells. Instead of plasmids, the second vaccine used another virus called an adenovirus as a carrier for a single HIV gene encoding a viral protein. The rationale for this combination was to employ a “safe” virus to catch the attention of immune cells while getting them to direct their responses against the HIV protein.

One of us (Weiner) had already been working on DNA vaccines for eight years and was hoping for a major demonstration of the plasmids’ ability to induce immunity against a dreaded pathogen. Instead the test results dealt a major blow to believers in this first generation of DNA vaccines. The DNA recipients displayed only weak immune responses to the five HIV proteins or no response at all, whereas recipients of the adenovirus-based vaccine had robust reactions. To academic and pharmaceutical company researchers, adenoviruses clearly looked like the stronger candidates to take forward in developing HIV vaccines.

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