Is Dengue Vaccine Protection Possible?

In tropical and subtropical countries, 4 dengue viruses (DENVs) produce mild disease and a potentially fatal vascular permeability syndrome. Unique antigenic and biological properties of DENVs contribute to vaccine development delays. Three tissue culture-based tetravalent candidate dengue vaccines have advanced to phase 3 clinical testing. Sanofi-Pasteur's chimeric yellow fever tetravalent dengue vaccine, Dengvaxia, licensed in 19 dengue-endemic countries, Europe, and the United States, partially protects seropositives but sensitizes some seronegatives to severe hospitalized dengue. During 2 years of phase 3, Takeda's TAK-003, a chimeric DENV 2 tetravalent vaccine, protected against DENV 2 but was less protective against other DENVs. In seronegative adults, 1 dose of a tetravalent nonstructural deletion mutant vaccine in late phase developed by the US National Institutes of Health protected seronegative humans against challenge with DENVs 2 and 3. This experience suggests nearly whole DENV genomes are required to achieve balanced and sustained protective immunity.