Study demonstrates long-term safety, immunogenicity of dengue vaccine
A tetravalent dengue vaccine candidate elicited long-term immune responses in children and adults in a phase 2 trial, with seropositivity rates of at least 88% for three of four serotypes 3 years after vaccination.
TAK-003 (Takeda) was well tolerated, with no reported serious adverse events, researchers reported in The Journal of Infectious Diseases.
In the first part of the randomized, placebo-controlled trial, Derek Wallace, vice president and global dengue program leader at Takeda, and colleagues enrolled 148 individuals aged 1.5 years to 45 years from four dengue-endemic countries — Puerto Rico, Columbia, Singapore and Thailand — into four age groups and randomly assigned them in a 2:1 ratio to receive two doses of TAK-003 or placebo 90 days apart. In the next part, they enrolled 212 children aged 1 to 11 years and randomly assigned them in a 3:1 ratio to receive the vaccine or placebo. According to the study, the researchers then assessed neutralizing antibody titers for the four dengue serotypes (DENV) and symptomatic dengue and serious adverse events up to 3 years.
According to the results, at month 36, seropositivity rates were 97.3%, 98.7%, 88% and 56% for DENV-1, -2, -3 and -4, respectively. Seropositivity rates for DENV-4 were 89.5% in participants who were seropositive at baseline but just 21.6% in participants who were seronegative, the researchers wrote.
Results of an ongoing phase 3 trial published last year suggested that TAK-003 is effective in children and adolescents aged 4 to 16 years.
According to Wallace, a 48-month analysis of the phase 2 DEN-204 trial published in The Lancet showed that antibody responses persisted for 48 months following all three dosing schedules of TAK-003 ⎼⎼ one primary dose; two primary doses administered 3 months apart; and one primary dose, followed by a booster dose 1 year later.
The trial “assessed the immunogenicity and safety of three different dosing schedules of TAK-003 or placebo over 48 months in children and adolescents living in dengue-endemic areas in Asia and Latin America. The completed study provides long-term data on antibody persistence and safety of TAK-003,” Wallace told Healio.
“Understanding the detailed characterization of immune responses after vaccination is an important part of the development program for TAK-003,” Wallace said. “The data from the phase 2 DEN-204 trial can help us to understand the mechanism of action of our vaccine candidate and predict its performance across different populations and geographies.”
The trial did not assess vaccine efficacy, but according to Wallace, a significantly lower risk for virologically confirmed dengue was demonstrated in the vaccine groups compared with the placebo group over the 4-year study period (RR = 0.35; 95% CI, 0.19-0.65) and the study identified no safety risks.
“Importantly, the results of the phase 2 DEN-204 trial support the choice of a two-dose schedule used in the phase 3 TIDES trial and provide insight into the long-term safety and antibody persistence of TAK-003,” Wallace said.
Last year, the FDA approved a different dengue vaccine, Dengvaxia (Sanofi Pasteur), for all four serotypes in children aged 9 through 16 years with laboratory confirmation of a previous dengue infection, but the CDC’s Advisory Committee on Immunization Practices still has not made recommendations for its use.
The vaccine is approved only for children with laboratory-confirmed previous dengue infection because it can act as an initial dengue infection, putting the recipient at risk for more serious disease if they have not been infected at least once previously and are infected again.
[Editor’s note: This story was updated to correctly place Wallace’s quotes about the DEN-204 trial.]
References:
- Sirivichayakul C, et al. J Infect Dis. 2020;doi:10.1093/infdis/jiaa406.
- Tricou V, et all. The Lancet. 2020;doi:10.1016/S0140-6736(20)30556-0.
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