An experimental dengue fever vaccine appears to be closer than ever to gaining approval for human use. According to the results of a large clinical trial — the third such trial the vaccine has undergone — receiving three doses of the vaccine reduces the overall risk of becoming infected with the tropical mosquito-borne disease by 60 percent. Moreover, the drug appears to be 95.5 percent protective against the most severe form of the disease, dengue hemorrhagic fever, which means that a widely-adopted vaccine could one day make a big dent in the number of dengue-related hospitalizations worldwide.
"There’s no vaccine for dengue currently, nor is there any specific treatment for managing illness in people who contract symptomatic dengue disease," says Alain Bernal, a spokesperson for Sanofi Pasteur, the drug’s manufacturer and the trial’s sponsor. "These results show that our candidate vaccine has the potential to have a major public health impact."
"Our candidate vaccine has the potential to have a major public health impact."
About 20,000 Latin American children between the ages of 9 and 16 were enrolled in the trial, published today in The New England Journal of Medicine. Of those children, 12,574 received three doses of the vaccine over the course of 12 months, while the rest of the children received a placebo. Results of the trial indicate that the vaccine was 60.8 percent effective against dengue, and that it reduced the risk of being hospitalized for dengue by 80.3 percent during the study’s 25-month surveillance period.
The "dengue vaccine does not work so well," says Jianzhu Chen, an immunologist at MIT. But it does appear to reduce hospitalization rates, he says, which means that it probably reduces the severity of dengue symptoms. "It’s the best dengue vaccine so far," Chen says, and its eventual approval "will be a milestone for tropical medicine after such a long effort."
The "dengue vaccine does not work so well."
When the trial's results were broken down by disease type, the vaccine offered a 95.5 percent protection against the most severe form of dengue during the 25-month period following vaccination. But that result wasn’t replicated for dengue serotypes I and II — less severe forms of dengue — where the efficacy rates were 50.3 percent and 42.3 percent, respectively. Still, Bernal says, "the study shows conclusive efficacy against each of the four dengue serotypes, including serotype II, which is indeed at the lower end compared to the other three serotypes."
Overall, the results were very similar to those found in previous trials. The researchers who conducted the first large clinical trial found that the vaccine was 56.6 percent effective against dengue, whereas results from a second clinical trial found that the vaccine reduced the incidence of dengue by 60.8 percent.
When the second trial’s results were released, Scott Halstead, scientific adviser to the nonprofit Dengue Vaccine Initiative, told The New York Times that the results were "not anywhere close to what we had hoped, something that would reach up into the 90s." And today, many researchers continue to express a need for a more effective vaccine.
Sanofi Pasteur will file for registration of the vaccine in 2015
"It is not a perfect vaccine yet, but a promising one," says Annelies Wilder-Smith, an epidemiologist at Nanyang Technological University in Singapore. "It is most important to protect against severe disease versus mild disease, so reduction by 95 percent is very good." Given these results, and those from the previous trials, she thinks the vaccine offers enough protection to warrant introduction into dengue endemic countries.
If everything goes according to plan, the vaccine’s introduction could happen soon. According to Bernal, Sanofi Pasteur plans to file for registration of the vaccine in 2015, in countries where dengue is prevalent. That means that "the world’s first dengue vaccine could be available in the second half of 2015," he says. And if the drug is eventually approved, the drug manufacturer says it will be able to supply one billion doses of the vaccine over 10 years — a number that Bernal says will "meet the need" observed in countries where dengue is endemic.