A phase 3 clinical trial found the Butantan-DV tetravalent dengue vaccine provided 80.5% protection against severe dengue with warning signs over 5 years and prevented hospitalizations among vaccinated participants.
A single-dose tetravalent dengue vaccine developed by the Butantan Institute in São Paulo demonstrated strong and sustained protection against severe dengue over five years in a large phase 3 clinical trial, according to results published March 4 in Nature Medicine.1 The vaccine, known as Butantan-DV, showed 80.5% effectiveness against severe dengue cases with warning signs, while also reducing symptomatic infections and preventing hospitalizations among vaccinated participants.2
The study enrolled 16,235 participants between the ages of 2 and 59 across 16 research centers in Brazil’s five geographic regions between February 2016 and July 2019. Of those participants, 10,259 received a single dose of the vaccine, while 5,976 received a placebo.2
During the 5-year monitoring period, no hospitalizations occurred among vaccinated participants, compared with eight hospitalizations in the placebo group, highlighting the vaccine’s potential to prevent severe outcomes from dengue infection.2
Overall, the vaccine demonstrated 65% effectiveness in preventing symptomatic dengue infections caused by any serotype during the follow-up period.2
The vaccine received regulatory approval from the Brazilian Health Regulatory Agency in November 2025 for individuals 12 to 59 years of age. Following approval, the Butantan Institute delivered 1.3 million doses to Brazil’s National Immunization Program, which distributes vaccines through the country’s public health system, the Sistema Único de Saúde.2
Brazil’s Ministry of Health has already begun implementing the vaccine through a pilot immunization campaign targeting 90% of eligible residents in the municipalities of Nova Lima, Maranguape, and Botucatu. Vaccination of primary care health professionals started in February as part of the rollout.2
The vaccine’s tetravalent design targets the four known dengue virus serotypes—DENV-1, DENV-2, DENV-3, and DENV-4—which circulate globally and can complicate immunity because infection with one serotype does not guarantee protection against the others.2
The Butantan-DV vaccine demonstrated 80.5% effectiveness against severe dengue with warning signs over five years.
No hospitalizations occurred among vaccinated participants, compared with eight in the placebo group.
The vaccine targets all four dengue serotypes, potentially simplifying immunization strategies in endemic regions.
Butantan-DV uses live attenuated viruses, meaning the viruses are weakened in the laboratory so they cannot cause disease but can still trigger an immune response. The strains used in the vaccine build on technology originally developed by the National Institutes of Health.2
The vaccine’s design incorporates nearly complete genomes for the DENV-1, DENV-3, and DENV-4 strains. For DENV-2, the vaccine uses a chimeric virus, combining DENV-2 surface proteins with the attenuated structural backbone of DENV-4.2
After vaccination, these attenuated viruses replicate in a controlled manner in the body, a process known as vaccine viremia, which stimulates the immune system to produce neutralizing antibodies against each dengue serotype. The goal is to establish targeted immunity so that the immune system can recognize and neutralize each variant individually if exposure occurs.2
Researchers say this broad immune response could help address the complex epidemiology of dengue, where infection with multiple serotypes contributes to disease burden and can increase the risk of severe illness.2
“This vaccine is establishing itself as a very important tool in the fight against dengue in Brazil, with the potential to contribute to reducing the circulation of the virus, in addition to individual protection,” Fernanda Boulos, medical director of clinical trials at the Butantan Institute, said in a statement.2
If widely implemented, the vaccine could play a significant role in controlling dengue transmission in endemic regions, particularly in Brazil, where seasonal outbreaks continue to strain public health systems.2
