The largest burden of dengue disease occurs in Southeast Asia and Central and South America. The New England Journal of Medicine published the results of a phase 3, double-blind trial conducted in Brazil, which evaluated the efficacy of the Butantan-Dengue Vaccine (Butantan-DV). This vaccine is a tetravalent, live attenuated candidate administered in a single dose and is under investigation for the prevention of dengue disease. The trial demonstrated that a single dose of Butantan-DV effectively prevented symptomatic DENV-1 and DENV-2 infections, regardless of the participants' initial dengue serostatus, over a follow-up period of 2 years.
During 3 years of enrollment, 16,235 participants were divided to receive either the investigational vaccine (10,259 participants) or a placebo (5,976 participants). The vaccine demonstrated an overall efficacy of 79.6% (95% confidence interval (CI), 70.0 to 86.3) over two years. Specifically, efficacy was 73.6% (95% CI, 57.6 to 83.7) among those without prior dengue exposure and 89.2% (95% CI, 77.6 to 95.6) among participants with previous exposure to the virus. In terms of age groups, vaccine efficacy was observed at 80.1% (95% CI, 66.0 to 88.4) in participants aged 2 to 6 years, 77.8% (95% CI, 55.6 to 89.6) in those aged 7 to 17 years, and 90.0% (95% CI, 68.2 to 97.5) in the 18 to 59-year-old cohort.
“Approximately half the participants in our trial did not have evidence of previous dengue exposure at baseline, which enabled robust assessments of vaccine efficacy and safety in this population,” wrote the investigators. “In the current trial, we enrolled a substantial percentage of participants without previous dengue exposure whom we plan to follow up for a projected 5 years in a country where dengue is endemic, thereby allowing a careful assessment of vaccine efficacy and safety in this population.”
The vaccine showed an efficacy of 89.5% (95% CI, 78.7 to 95.0) against DENV-1 and 69.6% (95% CI, 50.8 to 81.5) against DENV-2. There were no cases of DENV-3 and DENV-4 detected during the follow-up. Within 21 days following injection, solicited systemic adverse events related to either the vaccine or placebo were more frequent in the vaccine group than in the placebo group, affecting 58.3% of vaccine recipients compared to 45.6% of those given the placebo.
Main Takeaways
- The Butantan-DV demonstrated significant efficacy in preventing symptomatic dengue caused by DENV-1 and DENV-2 serotypes, with an overall efficacy rate of 79.6% over 2 years.
- The trial also assessed the safety of the vaccine, noting a higher incidence of solicited systemic adverse events in the vaccine group compared to the placebo within the first 21 days post-vaccination.
- Efficacy varied by serostatus and age, with particularly high efficacy (89.2%) among those with prior dengue exposure and strong protection in all age groups, including a 73% efficacy in children aged 2 to 6 years without previous exposure.
The trial aimed to assess the overall efficacy of the vaccine in preventing symptomatic, virologically confirmed dengue of any serotype that occurred more than 28 days post-vaccination without consideration of baseline serostatus. Additionally, it sought to evaluate safety up to day 21 post-vaccination. Vaccine efficacy was determined based on a 2-year follow-up period for each participant, while safety was evaluated through the reporting of solicited adverse events related to the vaccine within 21 days following the injection.
“The effect of dengue serostatus at baseline on vaccine efficacy and safety is particularly important for young children, who are less likely to have had previous dengue exposure at the time of vaccination,” wrote the investigators. “Approximately one-third of the participants were 2 to 6 years of age, 81% of whom had not had previous dengue exposure, which makes this age group an ideal target for vaccination to protect against first infection. After 2 years of follow-up, vaccine efficacy among children 2 to 6 years of age without previous dengue exposure was 73%, a finding which is like that in the older age groups.”
Limitations include the absence of DENV-3 and DENV-4 cases during the follow-up. The trial demonstrated protection against DENV-1 and DENV-2, which are often linked to more severe disease outcomes. The Zika outbreak might have influenced the lower dengue incidence observed from 2016 to 2018. Additionally, the low incidence of severe dengue cases limited the ability to conduct meaningful analyses and raised concerns about unblinding in this study. The reliance on serologic tests, which detect cross-reactive antibodies complicates the understanding of type-specific immunity’s effect on vaccine efficacy.
“The single-dose schedule of Butantan-DV was advanced to the current phase 3 trial,” investigators wrote. “A single dose of Butantan-DV offered protection against symptomatic, virologically confirmed dengue over the follow-up period. In previous trials, a second dose of Butantan-DV or TV003 given at 6 months or 12 months did not induce vaccine viremia or substantially boost antibody responses.”
This study demonstrated that a single dose of the investigational vaccine is safe and effective in preventing symptomatic, virologically confirmed dengue from DENV-1 and DENV-2, regardless of prior dengue exposure, over a 2-year follow-up period. The findings endorse the ongoing development of Butantan-DV as a preventive measure against dengue in both adults and children. Ongoing follow-up extending to 5 years will seek to provide more definitive long-term safety and efficacy data.
Reference
Kallás E, Cintra M, Moreira J, Patiño E, Braga P, et al. Live, attenuated, tetravalent butantan-dengue vaccine in children and adults. The New England Journal of Medicine. Published February 1, 2024. Access February 7, 2024. DOI: 10.1056/NEJMoa2301790
