The safety and effectiveness of the live, attenuated, tetravalent Butantan-DV vaccine were tested in adults, adolescents, and children. While initial results covered 2 years, this report extends to an average follow-up of 3.7 years. The vaccine was well tolerated and effective against symptomatic dengue caused by DENV-1 and DENV-2.1
Out of 16,363 participants assessed, 16,235 were randomly assigned between February 22, 2016, and July 5, 2019, to receive either Butantan-DV (10,259) or a placebo (5,976). Of these, 16,162 were included in the per-protocol analysis, and 16,235 in the safety analysis. By the data cutoff on July 13, 2021, participants had follow-up ranging from 2 to 5 years, with an average of 3.7 years.1
Main Takeaways
- The Butantan-DV vaccine achieved an overall efficacy of 79.6% against symptomatic dengue, showing strong protection across various age groups and serotypes.
- The vaccine's safety profile was comparable to the placebo, with similar rates of serious adverse events, though solicited systemic adverse events were more frequent in the vaccine group.
- Long-term follow-up of an average of 3.7 years confirms the Butantan-DV vaccine’s sustained effectiveness and supports its continued development for dengue prevention.
There were 356 confirmed dengue cases, with 128 in the vaccine group and 228 in the placebo group. The vaccine had 67.3% efficacy against dengue of any serotype, with no cases of virologically confirmed dengue (VCD)-3 or VCD-4. Serious adverse events were similar between groups: 6.2% in the vaccine group and 6.6% in the placebo group.1
In this double-blind, randomized, placebo-controlled, phase 3 trial in Brazil, healthy participants aged 2–59 who had not previously received a dengue vaccine were enrolled. They were randomly assigned to receive either 0.5 mL of Butantan-DV (containing four dengue virus strains) or a placebo. The syringes were prepared by an unmasked pharmacist, with site staff and participants unaware of the group allocations.1
Vaccine efficacy was assessed by the incidence of VCD cases at least 28 days after vaccination, with follow-up continuing for at least 2 years. The primary endpoint was vaccine efficacy against any dengue virus serotype. Safety was evaluated through primary and secondary endpoints, including unsolicited vaccine-related adverse events after day 22.1
Comparison
In the previous update from January 2024, found Butantan-DV a tetravalent, live attenuated candidate administered in a single dose and is under investigation for the prevention of dengue disease. The earlier summary reports an overall vaccine efficacy of 67.3% against symptomatic VCD of any serotype,2 while the new results show a higher overall efficacy of 79.6%. The new data further break down efficacy by previous dengue exposure, with 73.6% for those without prior exposure and 89.2% for those with prior exposure.1 Efficacy also varies by age group, ranging from 80.1% for ages 2-6 to 90.0% for ages 18-59.2 In terms of serotype-specific efficacy, the new results report 89.5% against DENV-1 and 69.6% against DENV-2.1
Regarding safety, the earlier summary focuses on serious adverse events, showing similar rates between the vaccine (6.2%) and placebo (6.6%) groups.2 In contrast, the new results provide information on solicited systemic adverse events within 21 days, which were more common with Butantan-DV (58.3%) compared to placebo (45.6%).1 Additionally, the earlier summary mentions an average follow-up period of 3.7 years,2 while the new results focus on a 2-year follow-up period without specifying the duration.1
Both summaries refer to the Butantan-DV vaccine and its administration to participants in a clinical trial. They both indicate that DENV-3 and DENV-4 were not detected or reported during the follow-up period. Additionally, both summaries address safety considerations, noting that adverse events were recorded for the vaccine group.
Overall, these findings support the continued development of Butantan-DV as a promising option for preventing dengue across all age groups. The vaccine's improved efficacy and safety profile make it a valuable candidate for broader use in dengue prevention.
References
Mogueira M, Cintra M, Moreira J, et. Al. Efficacy and safety of Butantan-DV in participants aged 2–59 years through an extended follow-up: results from a double-blind, randomised, placebo-controlled, phase 3, multicentre trial in Brazil. Lancet. Published August 5, 2024. Accessed August 7, 2024. DOI: https://doi.org/10.1016/S1473-3099(24)00376-1
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. Accessed August 7, 2024. DOI: 10.1056/NEJMoa2301790
