New Evidence in Phase 3 Trials Suggests Dengvaxia is Unsafe for Seronegative Patients

New Evidence in Phase 3 Trials Suggests Dengvaxia is Unsafe for Seronegative Patients

            A Phase 3 trial with Dengvaxia, the new tetravalent dengue vaccine produced by Sanofipasteur, has revealed significant problems with further use of the vaccine. The investigators watched 32,568 vaccinated and control children for hospitalizations and illness. They found that regardless of age, subjects seronegative for dengue virus who were vaccinated with Dengvaxia exhibited the patterns and clinical signs of antibody dependent enhanced (ADE) dengue disease. Though the vaccine has not shown major ill-effects in seropositive individuals, the fact that the vaccine can prime a patient for ADE severely limits its potential as a preventative measure, and will likely lead to its removal from the market in several areas.
               For decades, researchers have pursued a vaccine for dengue virus. The virus infects an estimated 390 million people annually, though it only causes severe disease in a relatively small percentage of that population. Nevertheless, the disease is estimated to kill around 25,000 people annually, and cause significant illness in millions of people.

Attempts to create a vaccine have been complicated by ADE, a phenomenon by which a dengue virus produces a more destructive infection in an individual who has previous been exposed to a different strain of dengue virus. There are four strains of dengue virus, and if a vaccine failed to immunize for one of them, it could heighten the risk for ADE. Now that Dengvaxia appears to do just that, researchers will need to find another way of preventing disease in at-risk individuals.

-Cole Holderman

            Sources:

1.       Article in Vaccine: Dengvaxia sensitizes seronegatives to vaccine enhanced disease regardless of age: http://www.sciencedirect.com/science/article/pii/S0264410X17313610?via%3Dihub

2.       WHO: Dengue Fever and Severe Dengue Disease: http://www.who.int/mediacentre/factsheets/fs117/en/

3.       World Mosquito Program: Eliminate Dengue: http://www.eliminatedengue.com/our-research/dengue-fever