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Florida Outbreak, Baltimore Trial

By Christen Brownlee

It’s no surprise that dengue fever makes seasonal appearances in Thailand, Vietnam, Brazil and other places where the disease is heavily entrenched. However, dengue recently reared its ugly head in a new place: Key West, Florida.

The CDC reported this summer that 5 percent of Key West’s residents had been exposed to the disease in 2009. Those findings make the efforts of International Health associate professor Anna Durbin very timely. Durbin plans to evaluate a live, attenuated vaccine to protect against the four viruses responsible for dengue. The first formulations of this vaccine, described in the Spring 2010 Johns Hopkins Public Health, have now entered phase 1 clinical trials, designed to test the safety and get an early read on effectiveness.

Starting in mid-July, Durbin, MD, and her colleagues began recruiting 84 volunteers, each of whom will receive one of three types of dengue vaccine or a placebo—neither the clinical staff or volunteers will know which one until the study’s end. The three formulations will test the volunteers’ response to slightly different strains of the four dengue-causing viruses.

An important difference between this vaccine and the five other dengue vaccines currently in development, explains Durbin, is all the up-front work that went into testing individual components before they were combined into a single vaccine. In earlier studies, researchers tested formulations containing just one of the four dengue viruses. “One thing we learned is that these four viruses don’t necessarily infect people equally well,” Durbin says. The first dengue-3 virus tested, in particular, showed a low level of infectivity, so the researchers searched for a more infective one. The higher the infectivity, she explains, the more likely those vaccinated will produce an effective immune response.

The new vaccine formulations combine these more infective strains with the other three viruses in “tetravalent” formulas administered to volunteers in a single shot designed to stimulate immunity to each of the viruses that causes dengue. Volunteers have reported every other day for the first 16 days of the trial. They had physical exams, were interviewed about side effects, and had blood drawn to track their immune systems’ responses to the vaccine. Over the next few months, these volunteers will continue to have blood tests to see whether any antibodies to the viruses multiply and whether immunity remains present for the long haul.

If this experiment is a success, it could lend hope not only to the people of countries where dengue has long been endemic but also to places like Key West where dengue is a new phenomenon. While few people became ill from the Florida outbreak, some researchers including Harold Margolis, chief of the CDC’s dengue branch, worry that the Keys might become an outpost for dengue, allowing it to migrate to other southern U.S. cities where the mosquito that transmits this disease can survive.

Margolis says that a vaccine would be useful in places where dengue has a strong foothold: “By vaccinating susceptible populations, you’ll ultimately prevent epidemics."