Public Release: 

Human challenge promises to speed up dengue vaccine development

American Association for the Advancement of Science

A controlled human challenge study shows that a candidate dengue vaccine can fully protect healthy volunteers who were intentionally infected with a weak form of the dengue virus. This type of study, among the first of its kind to be conducted for dengue, may offer a valuable tool for screening potential dengue vaccines before launching costly, and often risky, large-scale trials in dengue-endemic areas. The human challenge test could thus help speed up the development and guide the design of dengue vaccines, researchers say. Dengue is the most common mosquito-borne viral infection in the world, infecting 390 million people annually. While the virus usually causes no symptoms or only mild fever, more than 2 million people each year develop life-threatening dengue shock syndrome. Several candidate vaccines are currently in clinical trials. The path to the clinic is particularly arduous for dengue vaccines, which despite promising results in animals, often fail to prove protective in people. One of the biggest hurdles is that fact that a dengue vaccine must protect against all four serotypes of the dengue virus to be effective, because individuals previously infected with one serotype can suffer from worse disease symptoms when infected with another serotype. Thus, a vaccine that is only partially effective can potentially put people at even greater risk of severe dengue.

To better evaluate the protective efficacy of a live attenuated dengue vaccine called TV003, which recently completed phase 2 trials, Beth Kirkpatrick and colleagues conducted a randomized controlled study in a human challenge model, which has been used for studying malaria vaccines. Forty-one healthy individuals, who have not been previously exposed to dengue, received either a single shot of the vaccine or a placebo. They were then infected six months later with a weakened form of dengue serotype 2 virus, the hardest serotype to prevent. Whereas the 20 people in the placebo group developed mild symptoms like rash and low white blood cell count, all 21 vaccinated individuals developed none of these symptoms and were completely protected from infection. While only advanced clinical trials can establish a vaccine's efficacy, the researchers say, human challenge studies could help identify promising vaccine candidates and eliminate poor ones from progressing to larger trials. The results here support further evaluation of TV003, which is advancing to phase 3 trials in a dengue-endemic area early this year.


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