Safety and immunogenicity of a three dose regimen of two tetravalent live-attenuated dengue vaccines in five- to twelve-year-old Thai children

Objective. The safety and immunogenicity of tetravalent live-attenuated dengue vaccines after a three dose vaccination series were evaluated in Thai children. Method. One hundred three healthy flavivirus-seronegative schoolchildren ages 5 to 12 years were randomized to receive either dengue vaccine containing 3, 2, 1 and 2 log(10) of the 50% cell culture infective dose, respectively, of the live-attenuated dengue vaccine serotypes 1, 2, 3 and 4 per dose (F3212; n = 40) or 3, 3, 1 and 3 log(10) of the 50% cell culture infective dose (F3313; n = 42) or purified Vero cell rabies vaccine (control group; n = 21) given in a two dose schedule (3 to 5 months apart). A third dose was administered 8 to 12 months after the second dose to 90 subjects. Safety and immunogenicity were evaluated within 28 days after each injection. Results. No serious adverse event related to the vaccines occurred. Most children experienced mild to moderate fever, rash, headache and myalgia occurring within 12 days after Dose 1 and generally lasting 3 days or less. One subject in Group F3212 had a 1-week dengue-like fever. Reactogenicity was minimal after Doses 2 and 3. Transient mild variations in liver enzymes and hematologic indices were noted mainly after Dose 1. After the third dose 89% of the subjects in Group F3212 seroconverted (neutralizing antibody response, greater than or equal to10) to all four serotypes, and all children in Group F3313 seroconverted. Conclusion. This study demonstrates a moderate although improvable reactogenicity and high seroconversion rates against the four serotypes of dengue after a three dose schedule of tetravalent live-attenuated dengue vaccine in children.