In the Journals: A New Option for Preventing Dengue?

In 2019, the four serotypes of dengue virus caused an estimated 56 million cases and between 5,000 to 40,000 deaths in tropical countries. Typically, the first dengue infection causes a mild to moderate febrile illness of short duration. These initial infections provide lifelong protection against infection with the same serotype. However, second infections with a different serotype are responsible for much of the world’s severe and fatal illness due to a phenomenon called “antibody-dependent enhancement (ADE).”

The current vaccine, Dengvaxia, is composed of the yellow fever vaccine integrated chimerically with the structural regions of each of the four dengue serotypes. Unfortunately, Dengvaxia was complicated by severe disease following exposure to natural dengue due to the problem of ADE. For that reason, Dengvaxia, a three-dose vaccine, is recommended for people 9 years of age and older with clear evidence of at least one previous infection — the vaccine essentially serving as a second infection. Third and fourth infections are not complicated by ADE. Limiting Dengvaxia to those who were previously infected essentially eliminated the problem of ADE.

On Feb. 1, 2024, Kallas and coworkers reported the results of an investigational new single-dose dengue vaccine (Butantan-Dengue Vaccine, Butantan-DV) made by attenuating dengue types 1, 3, and 4; the type 2 component is a chimeric vaccine using the attenuated dengue type 4 containing structural elements of dengue type 2 (Kallas, EG, et al. Live, attenuated, tetravalent Butantan-Dengue Vaccine in children and adults. N Engl J Med. 2024 Feb 1;390(5):397-408). The vaccine was given to children and adults beginning at 2 years of age independent of whether participants had experienced a previous infection; 10,259 received the vaccine and 5,976 received a placebo. Follow-up was for two years. The overall efficacy was 79.6% in those with no previous history of exposure and 89.2% in those previously exposed to the virus. Vaccine efficacy was 80.1% in those 2 to 6 years of age, 77.8% in those 7 to 17 years of age, and 90% among those 18 to 59 years of age. No evidence of ADE was seen after this single-dose vaccine.

The live attenuated dengue viruses in Butantan-DV might provide longer-lived neutralizing antibodies, thus avoiding the problem of ADE found with the chimeric yellow fever vaccine, Dengvaxia. Scott Halsey, in an editorial (Three dengue vaccines — What now?) commenting on this vaccine wrote, “Clinical trials of Butantan-DV should be continued and, if possible, expanded.”