Dengue

A disease afflicting half a million people annually requires a special kind of vaccine

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Treatment: Live attenuated 17D yellow fever-dengue chimera Maker: Sanofi Pasteur Stage: Phase II, results scheduled for early 2008.

Why It Matters

Dengue fever, a mosquito-borne viral disease, and its life-threatening variant, dengue hemorrhagic fever, are probably the most widespread reemerging diseases worldwide. They hospitalize some 500,000 people annually, mostly children, and kill more than 20,000 per year. They are caused by one of four closely related viruses, each different enough that developing immunity against one guarantees nothing against the others. This means a successful vaccine has to be tetravalent, or combine four vaccines. Developing such a treatment is tricky, as the four vaccines can interact negatively with each other.

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How It Works

The two tetravalent vaccines furthest along in development are being pioneered separately by Sanofi Pasteur and an association of the Walter Reed Army Institute of Research (WRAIR) with GlaxoSmithKline (GSK). Both are weakened, or attenuated, live versions of the dengue viruses and are in phase II clinical trials. They both require two shots, and are supposed to build immunity after four to six months. Other than that, they are quite different: Sanofi Pasteur's researchers plugged sequences from the dengue viruses into a yellow fever vaccine virus, whereas the vaccine in development by WRAIR/GSK comes from dengue viruses cultured in the lab for generations until strains weak enough to be used in a vaccine emerged.

The vaccine Sanofi Pasteur is developing appears to be marginally further along in the development process, "but [these two vaccines] are at a stage where they are three weeks ahead one moment and six months behind another," says Harold Margolis, director of the Pediatric Dengue Vaccine Initiative. He cautions that dengue vaccine development is challenging--one vaccine from Mahidol University and Sanofi Pasteur that made it to phase II trials has already failed, generating side effects considered unacceptable for a commercial product.

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